Ionic liquids have many promising industrial applications. The side-chain length of the cations has been known to significantly influence the physical and chemical properties of those liquids, especially liquid crystal formation. 1 Because there are numerous species of possible ionic liquids, it is of great interest to understand the general physical picture behind the effect of varying the length of side chains of cations.In this work, a multiscale coarse-graining (MS-CG) method 2 has been extended to explore the effect of various cation side-chain lengths in ionic liquids. This method allows for large systems to be simulated for long times, thus revealing features of the system that are difficult to see using conventional all-atom molecular dynamics (MD) simulations. Simulations with the MS-CG models show that, with sufficient side-chain length, neutral tail groups of cations aggregate to form spatially heterogeneous domains of the tails, while the charged headgroups and anions distribute as uniformly as possible due to the strong electrostatic interactions. The geometrical constraints for head and tail groups of cations result in a novel balanced liquid crystal-like structure at suitable temperatures. This physical picture can qualitatively explain the experimentally observed ionic liquid crystal formation, the transition from liquid crystal to isotropic ionic liquid, and the changes of structural, dynamic, and thermodynamic properties when varying the sidechain length.The MS-CG method 2 has been applied here to the EMIM + NO 3 -ionic liquid to develop coarse-grained (CG) models at T ) 400 and 700 K, respectively. Details of the CG models are given in the Supporting Information. As shown in Figure 1, the nitrate anion has been coarse-grained as Site D, while the aromatic ring of the cation as Site A, the methyl group as Site B, the methylene and methyl groups on the alkyl chain as Sites C and E, respectively. To study the effect of chain-length elongation, the alkyl chain is then extended with two more methylene groups (Sites C) to form BMIM + NO 3 -. The partial charges are assigned as the numbers in Figure 1. The bonded parameters for the sites on the alkyl chain are assigned with the parameters for the sp 3 carbon (CT) sites given in ref 3. Although this model is a coarse-grained one, the qualitative results should not depend on the details of the force field parameters. For convenience, the ionic liquid systems will be denoted by the number of carbons on the alkyl chain, e.g., EMIM + NO 3 -as C 2 and BMIM + NO 3 -as C 4 . The C 4 MS-CG systems with 64, 400, and 800 ion pairs have been simulated by using the DL_POLY program 4 at T ) 700 K. The aggregation of tail groups was determined by visual examination for all three sizes of simulation. One snapshot of the simulation for 400 ion pairs is shown in Figure 2. Headgroups and anions are seen to distribute relatively homogeneously, but tail groups aggregate together and form several spatially heterogeneous domains.The heterogeneity of the tail groups is char...

The therapeutic effect of arsenic trioxide (As2O3 ) in the treatment of acute promyelocytic leukemia (APL) was evaluated among 15 APL patients at relapse after all-trans retinoic acid (ATRA) induced and chemotherapy maintained complete remission (CR). As2O3 was administered intravenously at the dose of 10 mg/d. Clinical CR was achieved in nine of 10 (90%) patients treated with As2O3 alone and in the remaining five patients treated by the combination of As2O3 and low-dose chemotherapeutic drugs or ATRA. During the treatment with As2O3 , there was no bone marrow depression and only limited side effects were encountered. Pharmacokinetic studies, which were performed in eight patients, showed that after a peak level of 5.54 μmol/L to 7.30 μmol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors. In addition, increased amounts of arsenic appeared in the urine, with a daily excretion accounting for approximately 1% to 8% of the total daily dose administered. Arsenic contents in hair and nail were increased, and the peak content of arsenic could reach 2.5 to 2.7 μg/g tissue at CR. On the other hand, a decline of the arsenic content in hair and nail was observed after withdrawal of the drug. We conclude that As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy.

The multiscale coarse-graining ͑MS-CG͒ method ͓S. Izvekov and G. A. Voth, J. Phys. Chem. B 109, 2469 ͑2005͒; J. Chem. Phys. 123, 134105 ͑2005͔͒ employs a variational principle to determine an interaction potential for a CG model from simulations of an atomically detailed model of the same system. The companion paper proved that, if no restrictions regarding the form of the CG interaction potential are introduced and if the equilibrium distribution of the atomistic model has been adequately sampled, then the MS-CG variational principle determines the exact many-body potential of mean force ͑PMF͒ governing the equilibrium distribution of CG sites generated by the atomistic model. In practice, though, CG force fields are not completely flexible, but only include particular types of interactions between CG sites, e.g., nonbonded forces between pairs of sites. If the CG force field depends linearly on the force field parameters, then the vector valued functions that relate the CG forces to these parameters determine a set of basis vectors that span a vector subspace of CG force fields. The companion paper introduced a distance metric for the vector space of CG force fields and proved that the MS-CG variational principle determines the CG force force field that is within that vector subspace and that is closest to the force field determined by the many-body PMF. The present paper applies the MS-CG variational principle for parametrizing molecular CG force fields and derives a linear least squares problem for the parameter set determining the optimal approximation to this many-body PMF. Linear systems of equations for these CG force field parameters are derived and analyzed in terms of equilibrium structural correlation functions. Numerical calculations for a one-site CG model of methanol and a molecular CG model of the EMIM + / NO 3 − ionic liquid are provided to illustrate the method.

Molecular dynamics simulations have been carried out to investigate nanostructural organization in mixtures of 1-octyl-3-methylimidazolium nitrate ionic liquid and water at multiple water concentrations. Evolution of the polar network, water network, and micelle structures is visualized and analyzed via partial radial distribution functions. The calculated static partial structure factors show that within the range of water contents examined, polar networks, water networks, and micelles possess an approximately invariant characteristic length at around 20 A. Furthermore, the above calculations point out that, as the amount of water increases, the polar network is continuously broken up (screened) by the intruding water, while the structural organization of the water network and the micelle exhibits a turnover. At the turnover point, the most ordered micelle (cation-cation) structure and water (water-anion-water) network are formed. Thereafter, the structural organization abates drastically, and only loose micelle structure exists due to the dominant water-water interactions. The simulated turnover of structural organization agrees with the sharpest peak in the experimentally obtained structure factor in aqueous solutions of similar ionic liquids; the simulated water structure reveals that water can form liquidlike associated aggregates due to the planar symmetry and strong basicity of NO(3)-, in agreement with experiment. The turnover of structural organization of micelles results from the persistent competition between the hydrophobic interactions of the nonpolar groups and the breakup of the charged polar network with increasing water content, whereas the turnover of the water network results from the competition between the water-water and water-anion interactions.

An extended multiscale coarse-graining model for ionic liquids is used to investigate the liquid crystal-like phase in certain ionic liquids. The tail groups of the cations with a sufficient side-chain length are found to aggregate, forming spatially heterogeneous domains, due to the competition between the electrostatic interactions between the charged head groups and the anions and the collective short-range interactions between the neutral tail groups. With a sufficiently long alkyl chain at a low enough temperature, the tail domains remain relatively stable, despite the diffusion of individual ions in the liquid phase. With increasing temperature, the average tail domains begin to diffuse, while beyond a transition temperature, their average density has an almost uniform distribution, although the tail groups still form instantaneous domains.