High-efficiency hydrophilic interaction chromatography by coupling 25 cm × 4.6 mm ID × 5 μm silica columns and operation at 80 °C

Recently, hydrophilic interaction chromatography (HILIC) has emerged as a valuable orthogonal tool to reversed-phase liquid chromatography (RP-LC) as it allows for resolution of highly polar ionisable compounds. The relationships between separation efficiency, column length and speed of analysis for 4.6 mm ID × 5 μm silica particle columns in HILIC are demonstrated using kinetic plots. The kinetic plots constructed for conventional pressure systems operating at 350 bar and at 30 °C and 80 °C are confirmed using experimental data for different column lengths. Efficiencies of more than 130,000 theoretical plates could be achieved by connecting up to six columns of 25 cm. As expected, a significant gain in analysis speed without loss of efficiency could be obtained by operating at 80 °C compared to 30 °C. The advantages of using long columns in HILIC in combination with elevated column temperature for the pharmaceutical industry are illustrated using test mixtures comprised of commercially available ionisable compounds (including some containing functional groups with potential genotoxic typical structural alerts) as well as real polar ionisable pharmaceuticals.     

Phase equilibrium measurements of structure II clathrate hydrates of hydrogen with various promoters

Phase equilibrium measurements of single and mixed organic clathrate hydrates with hydrogen were determined within a pressure range of 2.0-14.0 MPa. The organic compounds studied were furan, 2,5-dihydrofuran, tetrahydropyran, 1,3-dioxolane and cyclopentane. These organic compounds are known to form structure II clathrate hydrates with water. It was found that the addition of hydrogen to form a mixed clathrate hydrate increases the stability compared to the single organic clathrate hydrates. Moreover, the mixed clathrate hydrate also has a much higher stability compared to a pure hydrogen structure II clathrate hydrate. Therefore, the organic compounds act as promoter materials. The stabilities of the single and mixed organic clathrate hydrates with hydrogen showed the following trend in increasing order: 1,3-dioxolane < 2,5-dihydrofuran < tetrahydropyran < furan < cyclopentane, indicating that both size and geometry of the organic compound determine the stability of the clathrate hydrates.     

Ultrafast electron diffraction: excited state structures and chemistries of aromatic carbonyls

The photophysics and photochemistry of molecules with complex electronic structures, such as aromatic carbonyls, involve dark structures of radiationless processes. With ultrafast electron diffraction (UED) of isolated molecular beams it is possible to determine these transient structures, and in this contribution we examine the nature of structural dynamics in two systems, benzaldehyde and acetophenone. Both molecules are seen to undergo a bifurcation upon excitation (S(2)). Following femtosecond conversion to S(1), the bifurcation leads to the formation of molecular dissociation products, benzene and carbon monoxide for benzaldehyde, and benzoyl and methyl radicals for acetophenone, as well as intersystem crossing to the triplet state in both cases. The structure of the triplet state was determined to be "quinoidlike" of pipi(*) character with the excitation being localized in the phenyl ring. For the chemical channels, the product structures were also determined. The difference in photochemistry between the two species is discussed with respect to the change in large amplitude motion caused by the added methyl group in acetophenone. This discussion is also expanded to compare these results with the prototypical aliphatic carbonyl compounds, acetaldehyde and acetone. From these studies of structural dynamics, experimental and theoretical, we provide a landscape picture for, and the structures involved in, the radiationless pathways which determine the fate of molecules following excitation. For completeness, the UED methodology and the theoretical framework for structure determination are described in this full account of an earlier communication [J. S. Feenstra et al., J. Chem. Phys. 123, 221104 (2005)].     

SAR study of 1-aryl-4-(phenylarylmethyl)piperazines as ligands for both dopamine D2 and serotonin 5-HT1A receptors showing varying degrees of (Ant)agonism. Selection of a potential atypical antipsychotic

The syntheses of several 1-aryl-4-(arylpyridylmethyl)piperazines (4) and their affinities for dopamine D(2) and serotonin 5-HT(1A) receptors are described. The compounds were evaluated both in vitro and in vivo, resulting in the identification of the drug candidate SLV313 (4e) with equipotent and full D(2) receptor antagonism and 5-HT(1A) receptor agonism. Minor structural modifications in SLV313 revealed the possibility of designing compounds possessing varying degrees of partial agonism on one or both target receptors.     

A thermodynamic approach, using speciation studies, towards the evaluation and design of bone-seeking radiopharmaceuticals as illustrated for 117mSn(II)-PEI-MP

Blood plasma modeling has proved effective in the evaluation of clinical observations recorded for baboon and rat tests with ¹⁵³Sm- ethylenediaminetetraphosphonic acid (EDTMP) as well as for ¹⁶⁶Ho-EDTMP. In the search for a cure for metastatic bone cancer, ^117mSn with its conversion electrons of discrete energies shows low bone marrow toxicity, providing the opportunity to increase the administered dose. Selective accumulation in lesions would capitalize on this advantage. The 10-30 kDa fraction of the water-soluble polymer polyethyleneimine, functionalized with methylene phosphonate groups (PEI-MP) and labeled with ^99mTc, has shown selective uptake into bone tumours. This paper relates the speciation of Sn(II)-PEI-MP and other known ^117mSn(II) containing bone-seeking radiopharmaceuticals in blood plasma. Apparent formation constants for the complexation of Sn^II with PEI-MP, DTPA, HEDP and other important blood plasma ligands were measured potentiometrically or estimated by linear free energy relationships (LFER). These data were added to the ECCLES database in order to construct a blood plasma model for Sn^II. From this model it is predicted that Sn^II will remain bound to the polymer (PEI-MP) in blood plasma and therefore, have only slight reticuloendothelial uptake. Preliminary primate studies indeed proved that the complex between Sn^II and PEI-MP remains intact in blood plasma, which is consistent with the observation for PEI-MP labeled with ^99mTc. From these data, it was also possible to explain in retrospect the lower bone uptake, the slow blood clearance and the liver uptake of the agents ^117mSn(II) DTPA and ^117mSn(II) HEDP agents as reported in the literature.     

Nanolithography with metastable helium atoms in a high-power standing-wave light field

We have created periodic nanoscale structures in a gold substrate with a lithography process using metastable triplet helium atoms that damage a hydrophobic resist layer on top of the substrate. A beam of metastable helium atoms is transversely collimated and guided through an intense standing-wave light field. Compared to commonly used low-power optical masks, a high-power light field (saturation parameter of 10⁷) increases the confinement of the atoms in the standing wave considerably, and makes the alignment of the experimental setup less critical. Due to the high internal energy of the metastable helium atoms (20 eV), a dose of only one atom per resist molecule is required. With an exposure time of only eight minutes, parallel lines with a separation of 542 nm and a width of 100 nm (one-eleventh of the wavelength used for the optical mask) are created.PACS 32.80.Lg; 39.25.+k; 81.16.Nd     

Numerical simulations on the motion of atoms travelling through a standing-wave light field

The motion of metastable helium atoms travelling through a standing light wave is investigated with a semi-classical numerical model. The results of a calculation including the velocity dependence of the dipole force are compared with those of the commonly used approach, which assumes a conservative dipole force. The comparison is made for two atom guiding regimes that can be used for the production of nanostructure arrays; a low power regime, where the atoms are focused in a standing wave by the dipole force, and a higher power regime, in which the atoms channel along the potential minima of the light field. In the low power regime the differences between the two models are negligible and both models show that, for lithography purposes, pattern widths of 150 nm can be achieved. In the high power channelling regime the conservative force model, predicting 100 nm features, is shown to break down. The model that incorporates velocity dependence, resulting in a structure size of 40 nm, remains valid, as demonstrated by a comparison with quantum Monte-Carlo wavefunction calculations.Received: 11 December 2002, Published online: 29 July 2003PACS: 02.60.Cb Numerical simulation; solution of equations - 32.80.Lg Mechanical effects of light on atoms, molecules, and ions - 81.16.Rf Nanoscale pattern formationL. Feenstra: Present address: Physikalisches Institut, Universität Heidelberg, Philosophenweg 12, 69120 Heidelberg, Germany.