Molecular dynamics computer simulations are used to study hydrogen-bond structure and dynamics at the interface between water and carboxylic acid-functionalized self-assembled monolayers (CAFSAMs). Water-water, water-CAFSAM, and internal CAFSAM hydrogen bonds are examined. Roughly half of all adjacent carboxylic acid-terminated hydrocarbon chains are hydrogen-bonded to one another. This is consistent with experimental results reflecting two pKa values for CAFSAMs. Hydrogen-bond dynamics are expressed in terms of hydrogen-bond population autocorrelation functions and are found to be nonexponential. The water-water hydrogen-bond dynamics are slower at the interface than in the bulk, which is similar to what was found at the interface between water and weakly polar liquids such as nitrobenzene. The water-CAFSAM hydrogen bonds are found to be long-lived, on the order of tens of picoseconds. Internal CAFSAM chain-chain hydrogen bonds show almost no relaxation on the simulation time scale.

This Centennial Feature Article provides an overview of research in the general area of self-assembly modeling, with particular emphasis on the self-assembly of molecules into soft nanoscale structures where the driving force for assembly is provided by nonbonded interactions (hydrogen bonds and electrostatics). The models have been developed at many different levels of theory, going all the way from simple analytical models of packing effects to atomistic descriptions using molecular dynamics methods. In between these limits are mean-field and coarse-grained models, including models for DNA, peptides, and lipids that can be used to describe the assembly of hybrid (amphiphilic) materials. Several recent applications to specific systems are discussed, including the description of peptide amphiphile assembly to make cylindrical micelles, the assembly and melting of DNA hairpins, the use of DNA tethers to assemble nanoparticles into aggregates and crystalline structures, and the use of coarse-grained lipid models to make lamellar and high-curvature phases. These examples demonstrate the difficulties associated with brute force atomistic methods, and they also show the opportunities (but uncertainties and ambiguities) associated with simpler models such as coarse-grained models. The examples also demonstrate the usefulness of successful modeling methods in the design of new materials, including an understanding of the relationship between structure and function.

The ICN photodissociation reaction is the prototype system for understanding energy disposal and curve crossing in small molecule bond-breaking. The wide knowledge base on this reaction in the gas phase makes it an excellent test case to explore and understand the influence of a liquid solvent on the photo-induced reaction dynamics. Molecular dynamics simulations that include surface-hopping have addressed numerous aspects of how the solvent should influence non-adiabatic transitions and energy flow and ultimately determine product branching for this reaction system. In this paper, we report femtosecond transient absorption work directly combined with new molecular dynamics simulations that make direct connection with the spectroscopic observables. The full spectral evolution after initiating ICN photodissociation at 266 nm in water and ethanol is recorded with unprecedented time resolution, fast enough to see the nascent products emerge before interacting with the solvent cage. Use of a 266 nm pump maximizes the probability of subsequent caging on the upper diabat while launching large rotational energy release for trajectories emerging on the lower diabat. The 2D dataset yields a map of the different products and how they interconvert. In particular, information on the branching ratio and spectral evolution of the product bands is revealed as the products relax their electronic and rotational degrees of freedom. An evolution from rotationally hot gas-phase like CN (sharp band, at 390 nm) to equilibrated and solvated CN radicals (broad, at 326 nm in water and 415 nm in ethanol) is clearly observed in both solvents, and signals assignable to I* are also captured. The non-adiabatic molecular dynamics simulations focus on identifying when trajectories curve cross, filtering the trajectory ensemble into spectroscopically distinct sub-populations and analyzing the rotational energy for the CN product population. The experimental results, taken together with the MD simulations, establish the initial surface crossing probability and suggest multiple passes through the curve crossing region determine the final product yields and provide a source of freshly torqued CN radicals that continues to top up the population of rotationally hot photoproduct over the first few picoseconds.

The enhanced permeability of flat lipid bilayer membranes at their gel to liquid-crystalline (LC) phase transition has been explored using coarse-grained molecular dynamics. The phase transition temperature, T m , is deduced by monitoring the area per lipid, the lipid lateral diffusion constant, and the lipid-lipid radial distribution function. We find that a peak in the permeability coincides with the phase transition from the gel to LC state when lysolipid is present. This peak in permeability correlates with a jump in the area per lipid near the same temperature as well as increased fluctuations in the lipid bilayer free volume. At temperatures above T m , the permeability is only slightly dependent on the amount of lysolipid present. The increased free volume due to the "missing tail" of the lysolipid is partially compensated for by a decrease in area per lipid as the amount of lysolipid increases. We also found that in the coarse-grained model a small amount (≤15 mol %) of lysolipid stabilizes the gel phase and increases the phase transition temperature, while a larger amount of lysolipid (20 mol %) reduces T m back to that for pure DPPC, and bilayers consisting of ≥30 mol % lysolipid did not form a gel phase but still exhibited a peak in permeability near T m for pure DPPC.

A novel delivery system for the anticancer drug arsenic trioxide (ATO) is characterized. The release of ATO from DPPC liposomes with MPPC lysolipid incorporated into the bilayer is measured. There is negligible leakage of ATO from all systems at 25°C. Upon heating the liposomes to 37°C, there is 15% to 25% release over a 24 h time period. The ATO release from the DPPC and DPPC:MPPC(5%) systems levels off after 10 h at 37°C, whereas the DPPC:MPPC(10%) liposomes continue to release ATO over the 24 h timespan. Upon heating the liposomes rapidly to 42°C, through the gel to liquid-crystalline (LC) phase transition, the release rate is substantially increased. The two systems containing lysolipids, DPPC:MPPC(5%) and DPPC:MPPC(10%), exhibit a very rapid release of a significant amount of arsenic in the first hour. In the first hour, the DPPC:MPPC(5%) liposomes release 40% of the arsenic and the DPPC:MPPC(10%) liposomes release 55% of the arsenic. Arsenic release from pure DPPC liposomes is comparable at 37°C and 42°C, indicating presence of lysolipid is necessary for a significant enhancement of the release rate. A coarse-grained molecular dynamics (CGMD) model is used to investigate the enhanced permeability of lysolipid-incorporated liposomes and lipid bilayers. The CG liposomes did not form a gel phase when cooled due to the high curvature, however permeability was still significantly lower at 12°C, below what would be the liquid to gel phase transition temperature. At 50°C and 77°C, above Tm, we find water permeability coefficients on the order of 1.0×10−3 cm s−1, in good agreement with experiment. From simulations of flat DPPC:MPPC bilayers we find that a peak in the permeability does coincide with the phase transition from the gel to LC state when the lysolipid MPPC is present. No pores are observed in the simulations, however due to limitations in the model, we cannot rule out the possibility of lysolipid-stabilized pores enhancing the permeability in the experiments.