Stacking and Branching in Self-Aggregation of Caffeine in Aqueous Solution: From the Supramolecular to Atomic Scale Clustering

The dynamical and structural properties of caffeine solutions at the solubility limit have been investigated as a function of temperature by means of MD simulations, static and dynamic light scattering, and small angle neutron scattering experiments. A clear picture unambiguously supported by both experiment and simulation emerges: caffeine self-aggregation promotes the formation of two distinct types of clusters: linear aggregates of stacked molecules, formed by 2–14 caffeine molecules depending on the thermodynamic conditions and disordered branched aggregates with a size in the range 1000–3000 Å. While the first type of association is well-known to occur under room temperature conditions for both caffeine and other purine systems, such as nucleotides, the presence of the supramolecular aggregates has not been reported previously. MD simulations indicate that branched structures are formed by caffeine molecules in a T-shaped arrangement. An increase of the solubility limit (higher temperature but also higher concentration) broadens the distribution of cluster sizes, promoting the formation of stacked aggregates composed by a larger number of caffeine molecules. Surprisingly, the effect on the branched aggregates is rather limited. Their internal structure and size do not change considerably in the range of solubility limits investigated

Molecular Dynamics and Neutron Scattering Studies of Mixed Solutions of Caffeine and Pyridine in Water

Insight into the molecular interactions of homotactic and heterotactic association of caffeine and pyridine in aqueous solution is given on the basis of both experimental and simulation studies. Caffeine is about 5 times more soluble in a 3 <i>m</i> aqueous pyridine solution than it is in pure water (an increase from ∼0.1 <i>m</i> to 0.5 <i>m</i>). At this elevated concentration the system becomes suitable for neutron scattering study. Caffeine–pyridine interactions were studied by neutron scattering and molecular dynamics simulations, allowing a detailed characterization of the spatial and orientational structure of the solution. It was found that while pyridine–caffeine interactions are not as strong as caffeine–caffeine interactions, the pyridine–caffeine interactions still significantly disrupted caffeine–caffeine stacking. The alteration of the caffeine–caffeine stacking, occasioned by the presence of pyridine molecules in solution and the consequent formation of heterotactic interactions, leads to the experimentally detected increase in caffeine solubility

Comparison of Cellulose Iβ Simulations with Three Carbohydrate Force Fields

Molecular dynamics simulations of cellulose have recently become more prevalent due to increased interest in renewable energy applications, and many atomistic and coarse-grained force fields exist that can be applied to cellulose. However, to date no systematic comparison between carbohydrate force fields has been conducted for this important system. To that end, we present a molecular dynamics simulation study of hydrated, 36-chain cellulose Iβ microfibrils at room temperature with three carbohydrate force fields (CHARMM35, GLYCAM06, and Gromos 45a4) up to the near-microsecond time scale. Our results indicate that each of these simulated microfibrils diverge from the cellulose Iβ crystal structure to varying degrees under the conditions tested. The CHARMM35 and GLYCAM06 force fields eventually result in structures similar to those observed at 500 K with the same force fields, which are consistent with the experimentally observed high-temperature behavior of cellulose I. The third force field, Gromos 45a4, produces behavior significantly different from experiment, from the other two force fields, and from previously reported simulations with this force field using shorter simulation times and constrained periodic boundary conditions. For the GLYCAM06 force field, initial hydrogen-bond conformations and choice of electrostatic scaling factors significantly affect the rate of structural divergence. Our results suggest dramatically different time scales for convergence of properties of interest, which is important in the design of computational studies and comparisons to experimental data. This study highlights that further experimental and theoretical work is required to understand the structure of small diameter cellulose microfibrils typical of plant cellulose