ABSTRACT
A new proposal to obtain aggregation numbers from isothermal titration calorimetry dilution experiments is described and tested using dodecyl trimethyl ammonium bromide, dodecyl methylimidazolium chloride, dodecyl methylimidazolium sulfonate, and didecyl methylimidazolium chloride aqueous solutions at different temperatures. The results were compared to those obtained from fluorescence measurements and also with data from the literature. In addition to the aggregation number, the molar free energy to transfer a solute molecule from the aggregate to the bulk solution, the enthalpy corresponding to the formation of the self-assembled suprastructures, the molar heat corresponding to the dilution of monomers and aggregates, and an offset parameter to account for unpredictable external contributions are simultaneously obtained using the same method. The new equations are compared to those obtained from previous proposals, and they are also analyzed in detail to assess the impact of each fitting parameter in the profile of the calorimetric isotherm. This new approach has been implemented in a computational code that automatically determines the fitting parameters as well as the corresponding statistical uncertainties for the large variety of calorimetric profiles that have been tested. Given the high sensitivity of the dilution experiments to the aggregation number for relatively small assemblies, our approach is proposed also to quantify the oligomerization state of biomolecules such as proteins and peptides.
Subject(s)
Micelles , Proteins , Calorimetry , Solutions , ThermodynamicsABSTRACT
The basket-like geometry of cyclodextrins (CDs), with a cavity able to host hydrophobic groups, makes these molecules well suited for a large number of fundamental and industrial applications. Most of the established CD-based applications rely on trial and error studies, often ignoring key information at the atomic level that could be employed to design new products and to optimize their use. Computational simulations are well suited to fill this gap, especially in the case of CD systems due to their low number of degrees of freedom compared with typical macromolecular systems. Thus, the design and validation of solid and efficient methods to simulate and analyze CD-based systems is key to contribute to this field. The behavior of supramolecular complexes critically depends on the media where they are embedded, so the detailed characterization of the solvent is required to fully understand these systems. In the present work, we use the inclusion complex formed by two α-CDs and one sodium dodecyl sulfate molecule to test eight different parameterizations of the GROMOS and AMBER force fields, including several methods aimed to increase the conformational sampling in computational molecular dynamics simulation trajectories. The system proved to be extremely sensitive to the employed force field, as well as to the presence of a water/air interface. In agreement with previous experiments and in contrast to the results obtained with AMBER, the analysis of the simulations using GROMOS showed a quick adsorption of the complex to the interface as well as an extremely exotic behavior of the water molecules surrounding the structure both in the bulk aqueous solution and at the water surface. The chirality of the CD molecule seems to play an important role in this behavior. All together, these results are expected to be useful to better understand the behavior of CD-based supramolecular complexes such as adsorption or aggregation driving forces, as well as to introduce new methods able to speed up general MD simulations.