A fundamental understanding of the factors that determine the interactions with and transport of small molecules through phospholipid membranes is crucial in developing liposome-based drug delivery systems. Here we combine time-dependent second harmonic generation (SHG) measurements with molecular dynamics simulations to elucidate the events associated with adsorption and transport of the small molecular cation, malachite green isothiocyanate (MGITC), in colloidal liposomes of different compositions. The molecular transport of MGITC through the liposome bilayer is found to be more rapid in 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPG and DOPS, respectively) liposomes, while the molecular transport is slower in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes. Interestingly, MGITC is observed to neither adsorb nor transport in trimethyl quinone-1,2-dioleoyl-sn-glycero-3phosphoethanolamine (QPADOPE) liposomes due to shielding by the quinone group. The modified Langmuir adsorption isotherm model is used to determine the free energy of adsorption for MGITC, which is found to be less negative in DOPC than in DOPG and DOPS, caused by lower electrostatic interactions between the positively charged dye and the zwitterionic DOPC liposome surface. The results are compared to our previous investigations, which showed that malachite green (MG) adsorbs and transports in DOPG and DOPS liposomes but not in DOPC and QPADOPE liposomes. Molecular dynamics simulations are used to investigate the adsorption and transport properties of MG and MGITC in DOPC and DOPG liposomes using umbrella sampling to determine the free energy profiles and interfacial molecular orientations. Together, these timeresolved SHG studies and corresponding molecular dynamics simulations characterize the complicated chemical interactions at different lipid membranes to provide key molecular-level insights for potential drug delivery applications. The results also point toward understanding the role of chemical functional groups, in this case isothiocyanate, in controlling molecular adsorption at and transport through lipid bilayers.

The acid-mediated condensation of acetamide with butanal dimethylacetal and EtSCHCH(OMe), followed by dehydration, was investigated by electronic structure calculations that supported the prediction that the Z-geometry would be favored in the product. The reaction was investigated experimentally using suitably functionalized cysteine building blocks. Some side reactions and optimization of reaction conditions are reported, en route to identifying a mild, inexpensive Lewis acid that achieves a reasonable yield of (Z)-thioenamide 21 with high stereoselectivity.

The graphene oxide (GO)−water interface was simulated using Born− Oppenheimer molecular dynamics (BOMD) simulations with two different functionals, namely, revPBE-D3 and BLYP-D2, as well as a commonly used classical force field, namely, OPLS-AA. A number of different order parameters, including the orientation of the interfacial water molecules near the aromatic region of the GO surface as well as those near the oxygenated defects, were examined and compared. The BOMD interfacial waters are clearly much less structured as compared to the classical force field that shows a strongly ordered interface. Higher-level calculations, namely, symmetry adapted perturbation theory, were performed on representative clusters taken from the BOMD simulation. These calculations revealed not only that a number of conformations have similar interaction energies but also the importance of induction contribution to the interaction energies.

Sodium-based rechargeable battery technologies are being pursued as an alternative to lithium, in part due to the relative abundance of sodium compared to lithium. Despite their low dielectric constant, glyme-based electrolytes are particularly attractive for these sodium-based batteries due to their ability to chelate with the sodium ion and their high electrochemical stability. While the glyme chain length is a parameter that can be tuned to modify solvation properties, charge transport behavior, reactivity, and ultimately battery performance, anion identity provides another tunable variable. Trifluoromethanesulfonate (triflate/OTf) and bis(trifluoromethane)sulfonamide (TFSI) are chemically similar anions, which are often used in battery electrolytes for lithium-based batteries. In this paper, molecular simulations are used to examine the differences in ion association and charge transport between sodium salts of these two anions at different salt concentrations in glymes with the increasing chain length. The use of the modified force field developed for NaOTf in glymes for the NaTFSI electrolytes was validated by comparing the TFSI–sodium ion radial distribution functions to the results from ab initio molecular dynamics simulations on 1.5 M NaTFSI in diglyme. While the ion association behavior as a function of salt concentration showed similar trends for both NaOTf and NaTFSI in tetraglyme and triglyme electrolytes, the dominant solvation structures for the two sets of electrolytes are distinctly different in the monoglyme and diglyme cases. The conductivity is impacted by both the ion association behavior in these electrolytes and the non-vehicular or hopping transport of the anions in these systems.

A fundamental understanding of the kinetics and thermodynamics of chemical interactions at the phospholipid bilayer interface is crucial for developing potential drug-delivery applications. Here we use molecular dynamics (MD) simulations and surface-sensitive second harmonic generation (SHG) spectroscopy to study the molecular adsorption and transport of a small organic cation, malachite green (MG), at the surface of 1,2-dioleoyl- sn -glycero-3-phospho-(1′- rac -glycerol) (DOPG) liposomes in water at different temperatures. The temperature-dependent adsorption isotherms, obtained by SHG measurements, provide information on adsorbate concentration, free energy of adsorption, and associated changes in enthalpy and entropy, showing that the adsorption process is exothermic, resulting in increased overall entropy. Additionally, the molecular transport kinetics are found to be more rapid under higher temperatures. Corresponding MD simulations are used to calculate the free energy profiles of the adsorption and the molecular orientation distributions of MG at different temperatures, showing excellent agreement with the experimental results.