Elucidating solvent contributions to solution reactions with ab initio QM/MM methods.

Computer simulations of reaction processes in solution in general rely on the definition of a reaction coordinate and the determination of the thermodynamic changes of the system along the reaction coordinate. The reaction coordinate often is constituted of characteristic geometrical properties of the reactive solute species, while the contributions of solvent molecules are implicitly included in the thermodynamics of the solute degrees of freedoms. However, solvent dynamics can provide the driving force for the reaction process, and in such cases explicit description of the solvent contribution in the free energy of the reaction process becomes necessary. We report here a method that can be used to analyze the solvent contributions to the reaction activation free energies from the combined QM/MM minimum free-energy path simulations. The method was applied to the self-exchange S(N)2 reaction of CH(3)Cl + Cl(-), showing that the importance of solvent-solute interactions to the reaction process. The results were further discussed in the context of coupling between solvent and solute molecules in reaction processes.

The effect of hydrogen bonding on the diffusion of water in n-alkanes and n-alcohols measured with a novel single microdroplet method.

While the Stokes-Einstein (SE) equation predicts that the diffusion coefficient of a solute will be inversely proportional to the viscosity of the solvent, this relation is commonly known to fail for solutes, which are the same size or smaller than the solvent. Multiple researchers have reported that for small solutes, the diffusion coefficient is inversely proportional to the viscosity to a fractional power, and that solutes actually diffuse faster than SE predicts. For other solvent systems, attractive solute-solvent interactions, such as hydrogen bonding, are known to retard the diffusion of a solute. Some researchers have interpreted the slower diffusion due to hydrogen bonding as resulting from the effective diffusion of a larger complex of a solute and solvent molecules. We have developed and used a novel micropipette technique, which can form and hold a single microdroplet of water while it dissolves in a diffusion controlled environment into the solvent. This method has been used to examine the diffusion of water in both n-alkanes and n-alcohols. It was found that the polar solute water, diffusing in a solvent with which it cannot hydrogen bond, closely resembles small nonpolar solutes such as xenon and krypton diffusing in n-alkanes, with diffusion coefficients ranging from 12.5x10(-5) cm(2)/s for water in n-pentane to 1.15x10(-5) cm(2)/s for water in hexadecane. Diffusion coefficients were found to be inversely proportional to viscosity to a fractional power, and diffusion coefficients were faster than SE predicts. For water diffusing in a solvent (n-alcohols) with which it can hydrogen bond, diffusion coefficient values ranged from 1.75x10(-5) cm(2)/s in n-methanol to 0.364x10(-5) cm(2)/s in n-octanol, and diffusion was slower than an alkane of corresponding viscosity. We find no evidence for solute-solvent complex diffusion. Rather, it is possible that the small solute water may be retarded by relatively longer residence times (compared to non-H-bonding solvents) as it moves through the liquid.

Probing polarization and dielectric function of molecules with higher order harmonics in scattering-near-field scanning optical microscopy

The idealized system of an atomically flat metallic surface [highly oriented pyrolytic graphite (HOPG)] and an organic monolayer (porphyrin) was used to determine whether the dielectric function and associated properties of thin films can be accessed with scanning-near-field scanning optical microscopy (s-NSOM). Here, we demonstrate the use of harmonics up to fourth order and the polarization dependence of incident light to probe dielectric properties on idealized samples of monolayers of organic molecules on atomically smooth substrates. An analytical treatment of light/sample interaction using the s-NSOM tip was developed in order to quantify the dielectric properties. The theoretical analysis and numerical modeling, as well as experimental data, demonstrate that higher order harmonic scattering can be used to extract the dielectric properties of materials with tens of nanometer spatial resolution. To date, the third harmonic provides the best lateral resolution (∼50 nm) and dielectric constant contrast for a porphyrin film on HOPG. © 2009 American Institute of Physics.

Phase transfer catalysts drive diverse organic solvent solubility of single-walled carbon nanotubes helically wrapped by ionic, semiconducting polymers.

Use of phase transfer catalysts such as 18-crown-6 enables ionic, linear conjugated poly[2,6-{1,5-bis(3-propoxysulfonicacidsodiumsalt)}naphthylene]ethynylene (PNES) to efficiently disperse single-walled carbon nanotubes (SWNTs) in multiple organic solvents under standard ultrasonication methods. Steady-state electronic absorption spectroscopy, atomic force microscopy (AFM), and transmission electron microscopy (TEM) reveal that these SWNT suspensions are composed almost exclusively of individualized tubes. High-resolution TEM and AFM data show that the interaction of PNES with SWNTs in both protic and aprotic organic solvents provides a self-assembled superstructure in which a PNES monolayer helically wraps the nanotube surface with periodic and constant morphology (observed helical pitch length = 10 ± 2 nm); time-dependent examination of these suspensions indicates that these structures persist in solution over periods that span at least several months. Pump-probe transient absorption spectroscopy reveals that the excited state lifetimes and exciton binding energies of these well-defined nanotube-semiconducting polymer hybrid structures remain unchanged relative to analogous benchmark data acquired previously for standard sodium dodecylsulfate (SDS)-SWNT suspensions, regardless of solvent. These results demonstrate that the use of phase transfer catalysts with ionic semiconducting polymers that helically wrap SWNTs provide well-defined structures that solubulize SWNTs in a wide range of organic solvents while preserving critical nanotube semiconducting and conducting properties.

Stereocomplexed poly(lactic acid)-poly(ethylene glycol) nanoparticles with dual-emissive boron dyes for tumor accumulation.

Responsive biomaterials play important roles in imaging, diagnostics, and therapeutics. Polymeric nanoparticles (NPs) containing hydrophobic and hydrophilic segments are one class of biomaterial utilized for these purposes. The incorporation of luminescent molecules into NPs adds optical imaging and sensing capability to these vectors. Here we report on the synthesis of dual-emissive, pegylated NPs with "stealth"-like properties, delivered intravenously (IV), for the study of tumor accumulation. The NPs were created by means of stereocomplexation using a methoxy-terminated polyethylene glycol and poly(D-lactide) (mPEG-PDLA) block copolymer combined with iodide-substituted difluoroboron dibenzoylmethane-poly(L-lactide) (BF2dbm(I)PLLA). Boron nanoparticles (BNPs) were fabricated in two different solvent compositions to study the effects on BNP size distribution. The physical and photoluminescent properties of the BNPs were studied in vitro over time to determine stability. Finally, preliminary in vivo results show that stereocomplexed BNPs injected IV are taken up by tumors, an important prerequisite to their use as hypoxia imaging agents in preclinical studies.

The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease.

Thymic graft-versus-host disease (tGVHD) can contribute to profound T cell deficiency and repertoire restriction after allogeneic BM transplantation (allo-BMT). However, the cellular mechanisms of tGVHD and interactions between donor alloreactive T cells and thymic tissues remain poorly defined. Using clinically relevant murine allo-BMT models, we show here that even minimal numbers of donor alloreactive T cells, which caused mild nonlethal systemic graft-versus-host disease, were sufficient to damage the thymus, delay T lineage reconstitution, and compromise donor peripheral T cell function. Furthermore, to mediate tGVHD, donor alloreactive T cells required trafficking molecules, including CCR9, L selectin, P selectin glycoprotein ligand-1, the integrin subunits alphaE and beta7, CCR2, and CXCR3, and costimulatory/inhibitory molecules, including Ox40 and carcinoembryonic antigen-associated cell adhesion molecule 1. We found that radiation in BMT conditioning regimens upregulated expression of the death receptors Fas and death receptor 5 (DR5) on thymic stromal cells (especially epithelium), while decreasing expression of the antiapoptotic regulator cellular caspase-8-like inhibitory protein. Donor alloreactive T cells used the cognate proteins FasL and TNF-related apoptosis-inducing ligand (TRAIL) (but not TNF or perforin) to mediate tGVHD, thereby damaging thymic stromal cells, cytoarchitecture, and function. Strategies that interfere with Fas/FasL and TRAIL/DR5 interactions may therefore represent a means to attenuate tGVHD and improve T cell reconstitution in allo-BMT recipients.