Sparsomycin analogs. VI. Synthesis and antitumor activity of octylsparsomycin analogs

Five sparsomycin analogs (9-13) were prepared and examined for their ability to inhibit deoxyribonucleic acid (DNA) synthesis in L5178Y lymphoma cells. All of the compounds showed significant activity in the DNA synthesis assay. The compounds having Rc configuration exhibited almost the same activities independently of the configuration at the sulfoxide sulfur atom. Among the Sc isomers, the Rs configuration was advantageous for the appearance of activity.     

Energetics, transition states, and intrinsic reaction coordinates for reactions associated with O(3P) processing of hydrocarbon materials

Electronic structure calculations based on multiconfiguration wave functions are used to investigate a set of archetypal reactions relevant to O(3P) processing of hydrocarbon molecules and surfaces. These include O(3P) reactions with methane and ethane to give OH plus methyl or ethyl radicals, O(3P) + ethane to give CH3O + CH3, and secondary reactions of the OH product radical with ethane and the ethyl radical. Geometry optimization is carried out with CASSCF/cc-pVTZ for all reactions, and with CASPT2/cc-pVTZ for O(3P) + methane/ethane. Single-point energy corrections are applied with CASPT2, CASPT3, and MRCI + Q with the cc-pVTZ and cc-pVQZ basis sets, and the energies extrapolated to the complete basis set limit (CBL). Where comparison of computed barriers and energies of reaction with experiment is possible, the agreement is good to excellent. The best agreement (within experimental error) is found for MRCI + Q/CBL applied to O(3P) + methane. For the other reactions, CASPT2/CBL and MRCI + Q/CBL predictions differ from experiment by 1-5 kcal/mol for 0 K enthalpies of reaction, and are within 1 kcal/mol of the best-estimate experimental range of 0 K barriers for O(3P) + ethane and OH + ethane. The accuracy of MRCI + Q/CBL is limited mainly by the quality of the active space. CASPT2/CBL barriers are consistently lower than MRCI + Q/CBL barriers with identical reference spaces.     

Effect of solvation on the dynamics of H + CH3 association

The gas phase association of CH₃ with the HAr₂ cluster to form a vibrationally/rotationally excited CH ₄ ^* molecule is used as a model to study microscopic solvation dynamics. A potential energy surface for the reactive system is constructed from a previously fitted H + CH₃ ab initio potential and 12-6 Lennard-Jones Ar-Ar, Ar-C, and Ar-H potentials. Classical trajectory calculations performed with the chemical dynamics computer program VENUS are used to investigate the CH₃ + HAr₂ → CH ₄ ^* + Ar₂ reaction dynamics. Reaction is dominated by a mechanism in which the CH₃ “strips” the H-atom from HAr₂ during large impact parameter collisions. For a large initial relative translational energy the CH₃ + HAr₂ → CH ₄ ^* + Ar₂ cross section is the same as that for H + CH₃ association, so that HAr₂ acts like a “heavy” H-atom. However, at a low initial relative translational energy, the long-range Ar₂—CH₃ attractive potential apparently makes the CH₃ + HAr₂ association cross section larger than that for H + CH₃. Partitioning of energy to the CH ₄ ^* and Ar₂ products is consistent with a stripping mechanism. The initial and final relative translational energies are nearly identical and the CH ₄ ^* rotational energy is controlled by the initial CH₃ rotational energy. The velocity and orbital tilt scattering angles, θ(v _i ,v _f ) and θ(l _i ,l _f ), respectively, are consistent with the stripping mechanism. On average only a small amount of the product energy is partitioned to Ar₂ vibration/rotation and CH ₄ ^* + Ar₂ relative translation.     

The infrared and Raman spectra of pyromellitic dianhydride

The infrared and Raman spectra of solid state samples of pyromellitic dianhydride have been measured. The infrared—Raman mutual exclusion rule has been observed and the frequencies have been tentatively assigned on the basis of D_2h symmetry. The values of the CO and skeletal ring stretching frequencies have been interpreted in terms of a conjugated π-system.     

Reaction products with internal energy beyond the kinematic limit result from trajectories far from the minimum energy path: an example from H + HBr --> H2 + Br

The importance of reactive trajectories straying far from the minimum energy path is demonstrated for the bimolecular reaction H + HBr --> H2(v', j') + Br at 53 kcal/mol collision energy. Product quantum state distributions are measured and calculated using the quasi-classical trajectory technique, and the calculations indicate that highly internally excited H2 products result from indirect reactive trajectories with bent transition states. A general argument is made suggesting that reaction products with internal energy exceeding a kinematic constraint can, in general, be attributed to reactive collisions straying far from the minimum energy path.     

Hydrogen molecules trapped in irradiated solid ethanol

Raman spectroscopy of γ-irradiated solid ethanol at 77 K revealed that trapped H₂ is produced mainly by the H atom abstraction at the alkyl group by H radicals which are dissociated from the alkyl group of ethanol. Comparison of the peak wavenumbers and the band widths of H₂ between the glassy and crystalline phases of ethanol suggests that the trapping sites of H₂ in the glassy phase are smaller in the average size and less homogeneous in the size distribution. The molar ratio between ortho- and para-H₂ trapped in irradiated crystalline ethanol is in rough agreement with the thermodynamic equilibrium between 5–120 K, intimating that the ortho-para conversion is allowed under the existence of an electro-magnetic gradient due to paramagnetic radicals.     

Site-specific carbohydrate profiling of human transferrin by nano-flow liquid chromatography/electrospray ionization mass spectrometry

Glycopeptides derived from a lysylendopeptidase digest of commercially available human transferrin were analyzed by nano-flow liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS), which permitted the carbohydrate profiles at Asn432 and Asn630 to be determined. Both are located in a well-known motif for N-glycosylation, Asn-Xaa-Ser/Thr. The contents of the carbohydrates at each site were significantly different from each other, and consisted of a variety of minor types of oligosaccharides in addition to the major one, a biantennary complex-type oligosaccharide. Nano-flow ESI tandem mass spectrometry (MS/MS) of the glycopeptides (Cys421-Lys433 and Ile619-Lys646) containing these two sites yielded predominantly ions originating from the non-reducing termini (oxonium ions) and reducing terminus, resulting from cleavage of the glycosidic bonds of the carbohydrate moieties; this permitted the structural read-out of a small minority of the carbohydrate moieties. In particular, the observation of oxonium ions at m/z 512.2 and 803.2 is useful for probing outer non-reducing terminal fucosylation, which represented carbohydrate structures consisting of Hex, dHex, and HexNAc, and NeuNAc, Hex, dHex, and HexNAc, respectively, from which the Lewis X structure (Galbeta1-4(Fucalpha1-3)GlcNAc) was readily deduced. Moreover, fucosylation at the reducing-terminal GlcNAc (Fucalpha1-6GlcNAc) specifically occurred at Asn630, as demonstrated by treatment of the glycopeptides with alpha1-3/4-L-fucosidase.     

A washboard with moment of inertia model of gas-surface scattering

A washboard with moment of inertia (WBMI) model for gas atom scattering from a flexible surface is proposed and applied. This model is a direct extension of the washboard model [J. Chem. Phys. 92, 680 (1990)] proposed for gas atom scattering from relatively rigid, corrugated surfaces. In addition, a moment of inertia is incorporated in the original washboard model to describe the flexibility of softer, more highly corrugated surfaces such as polymer or liquid surfaces. The moment of inertia of the effective surface object introduces a dependence of the efficiency of energy transfer on the position and direction of impact, a feature that has been shown to be critical by molecular dynamics simulations. The WBMI model is solved numerically by Monte Carlo integration, which makes the implementation of multiple impacts between a colliding atom and the surface very efficient. The model is applied to Ne and Ar atoms scattering from an alkylthiolate self-assembled monolayer surface and reproduces the major results obtained by classical trajectory simulation of the same system, i.e., a bimodal translation energy distribution P(E(f)) with the low-energy component well-fit with a Boltzmann distribution, but with a temperature that may (Ar) or may not (Ne) be the same as the surface temperature. This indicates that the WBMI model, with well-motivated physical assumptions and simplified interaction, reveals many of the major aspects of the gas-surface collision dynamics, though it does not take into account the real-time dynamics explicitly.     

Sensitivity of the H + CH3 → CH4 recombination rate constant to the shape of the CH stretching potential

Using a potential-energy surface obtained in part from ab initio calculations, the H + CH₃ → CH₄ bimolecular rate constant at T = 300 K is determined from a Monte Carlo classical trajectory study. Representing the CH stretching potential with a standard Morse function instead ofthe ab initio curve increases the calculated rate constant by an order of magnitude. The experimental recombination rate constant is intermediate of the rate constants calculated with the Morse and ab initio stretching potentials.Two properties of the H + CH₃ α CH₄ potential-energy surface which significantly affect the recombination rate constant are the shape of the CH stretching potential and the attenuation of the H₃CH bending frequencies. Ab initio calculations with a hierarchy of basis sets and treatment of electron correlation indicate the latter is properly described [13]. The exact shape of the CH stretching potential is not delineated by the ab initio calculations, since the ab initio calculations are not converged for bond lengths of 2.0–3.0 Å [12]. However, the form of this stretching potential deduced from the highest-level ab initio calculations, and fit analytically by eq. (2), is significantly different from a Morse function. The experimental recombination rate constant is intermediate of the rate constants calculated with the Morse and ab initio CH stretching potentials. This indicates that the actual CH potential energy curve lies between the Morse and ab initio curves. This is consistent with the finding that potential energy curves for diatomics are not well described by a Morse function [12].     

Colloidal crystals of core–shell-type spheres in deionized aqueous suspension

The structure, crystal growth kinetics and rigidity of colloidal crystals of core–shell-type latex spheres (diameters 280–330 nm) with differences in shell rigidity have been studied in aqueous suspension, mainly by reflection spectroscopy. The suspensions were deionized exhaustively for more than 2 years using mixed-bed ion-exchange resins. The five kinds of core–shell spheres examined form colloidal crystals, where the critical sphere concentrations, _c, of crystallization (or melting) are high and range from 0.01 to 0.06 in volume fraction. Nearest-neighbor intersphere distances in the crystal lattice agree satisfactorily with values calculated from the sphere diameter and concentration. The crystal growth rates are between 0.1 and 0.3 s^–1 and decrease slightly as the sphere concentration increases, indicating that the crystal growth rates are from the secondary process in the colloidal crystallization mechanism, corresponding to reorientation from metastable crystals formed in the primary process and/or Ostwald-ripening process. The rigidities of the crystals range from 2 to 200 Pa, and increase sharply as the sphere concentration increases. The g factor, the parameter for crystal stability, is around 0.02 irrespective of the sphere concentration and/or the kind of core–shell sphere. There are no distinct differences in the structural, kinetic and elastic properties among the colloidal crystals of the different core–shell-type spheres, showing that the internal sphere structure does not affect the properties of the colloidal crystals. The results show that colloidal crystals form in a closed container owing to long-range repulsive forces and the Brownian movement of colloidal spheres surrounded by extended electrical double layers and that their formation is not influenced by the rigidity and internal structure of the spheres.