The hydration structure in aqueous solutions of three tetraalkylammonium halides (TAAX), tetramethylammonium chloride (TMACl), tetrapropylammonium bromide (TPABr), and tetrabutylammonium bromide (TBABr) at concentrations of 2.2, 1.4, and 1.0 m, respectively, is studied via molecular dynamics (MD) simulation at ambient conditions. The results are compared directly with neutron diffraction with isotopic substitution (NDIS) experimental results for the same systems. In agreement with the NDIS results, we find evidence of a small enhancement of water structure around the apolar solutes, based on water H−H radial distribution functions. Decomposition of the water−water O−H radial distribution function into hydrogen-bonded and non-hydrogen-bonded components, using the geometric criterion for hydrogen bonding of Mezei and Beveridge (1981), allowed us to calculate the hydrogen-bonded (HB) contribution to the total O−H radial distribution function, both in the bulk solution and in the first solvation shell of the cations. For the TPA and TBA cations, there is a small enhancement in the probability of forming hydrogen bonds between solvation shell water molecules, while the reverse is true for TMA. We find that the HB contribution to the total O−H coordination number remains approximately constant in going from pure water to the TAAX solutions. An analysis of the distributions of the parameters of the hydrogen-bonding criterion between pure water and water in the first solvation shells of the cations reveals that there is a slight tendency for the water in the first solvation shell to form more “ideal” hydrogen bonds compared to pure water, particularly for the the larger cations. However, the differences in the water−water structure between TPA and TBA are negligibly small.

We describe a molecular dynamics simulation study of a model of the reversed-phase chromatographic system. The model consists of a slab of aqueous solvent sandwiched between two walls having attached C8 hydrocarbon chains at a surface coverage of 5.09 μmol/m2 or 32.6 A°2/chain. Long-ranged Coulombic interactions are taken into account using the Ewald sum method of Rhee et al. [Phys. Rev. B 1989, 40, 36]. The density and solvent orientation profiles are computed as a function of distance from the walls. The density profiles are found to be sensitive to the treatment of the long-ranged electrostatic interactions. The presence of an organic cosolvent (methanol or acetonitrile) at 30.8 mol % has little effect on the chain structure, which is largely collapsed against the walls. We also estimate the change in residual Helmholtz free energy along the pore width for a methane solute in the acetonitrile/water system, which indicates that a substantial portion of the free energy driving force for retention occurs in an organic-rich layer of solvent adsorbed to the hydrocarbon phase.

In vitro studies of zidovudine (ZDV) phosphorylation may not accurately reflect the in vivo dose-response relationship, which is crucial to determining the relationship between ZDV exposure, efficacy, and toxicity. However, measurement of ZDV phosphorylated anabolites in peripheral blood mononuclear cells (PBMCs) from ZDV-treated human immunodeficiency virus (HlV)-infected patients would be extremely useful in the more appropriate utilization of ZDV in the treatment of H1l infection. We developed a specific and sensitive combined high-pressure liquid chromatography (HPLC)-radioimmunoassay (RLA) procedure for the determination of ZDV, ZDV-monophosphate, ZDV-diphosphate, and ZDV-triphosphate in PBMCs taken from ZDV-treated HIV-infected patients. ZDV and its anabolites were extracted from washed, Ficoll-Paque-isolated PBMCs and then separated by HPLC using a strong anion-exchange column. 3'-Azido-3'-deoxythymidine (zidovudine) (ZDV) is a pyrimidine analog first synthesized in the mid 1960s (7) and shown to be active against human immunodeficiency virus (HIV) in 1985 (10). ZDV prolongs survival and reduces the rate of disease progression in HIV-infected patients (5). However, like several other anti-HIV nucleoside analogs, it is a prodrug and requires intracellular anabolic phosphorylation to be converted into its active form. ZDV enters cells by diffusion (8), after which it is first converted by a cellular thymidine kinase to ZDV-monophosphate (ZDV-MP). The ZDV-MP is then further phosphorylated by a cellular thymidylate kinase to ZDV-diphosphate (ZDV-DP). Although thymidylate kinase has a high affinity for ZDV-MP, it also has a low maximum rate of metabolism for its conversion to ZDV-DP, thus making conversion of ZDV-MP to ZDV-DP the rate-limiting reaction in the anabolic pathway (6). ZDV-DP is then further anabolized by other cellular nucleoside diphosphate kinases to ZDV-triphosphate (ZDV-TP). ZDV