This work presents results, aimed at identifying the crystallization mechanism of surfactant-stabilized hexadecane-in-water droplet with 15 nm diameter at the molecular level. The question is addressed by atomistic molecular dynamics simulations of models consisting of ca. 2 million atoms. To represent as closely as possible real-world systems, a procedure for constructing droplets of different sizes is developed, allowing control of the surfactant surface coverage. Two crystallization protocols are applied: slow freezing, in which the surface solidifies first, followed by relaxation and subsequent cooling to induce crystallization in the bulk, and fast freezing, in which the droplet is directly cooled to the final temperature, leading to simultaneous surface and core crystallization. A few key results may be outlined. The droplet surface always freezes first. Nucleation occurs stochastically at multiple independent sites, gradually propagating over the surface. Both shell and core undergo heterogeneous nucleation initiated by surfactant molecules. The nuclei in the core typically form close to the surface. The cooling procedure affects the spatial freezing pathway and molecular ordering in the drop core. The preferred orientation of bulk crystallites relative to the originating surface is nearly perpendicular. Once solidified, the surface alone is sufficient to induce droplet deformation to a triangular prism-like shape, additionally stabilized by the bulk crystallites. The deformation is a clear indication of a rotator phase, stable over hundreds of nanoseconds, further confirmed by the fraction of gauche conformations, P2 order parameters, and radial distribution functions. These findings agree with and complement experimental data and provide molecular-level verification of the experimentally observed fundamental difference in the stability of hexadecane rotator phase: transient in bulk and stable under micro- and nanoconfinement. This is the fundamental knowledge on microscopic freezing mechanisms of hexadecane and similar even-parity alkane-based materials at interfaces.

Introduction: The use of intravenous fat emulsions for treatment of drug intoxication still follows
a trial-and-error approach, due to insufficient understanding of the mechanisms of the process
and lack of predictive in vitro tools.

The effect of twelve cyclic molecules on the rheological response of a 10 wt% mixture of sodium lauryl ether sulfate and cocoamidopropyl betaine (BS) was evaluated. The results demonstrate that all studied additives effectively reduced the salt concentration required to reach peak viscosity and narrowed the width of the salt curve. The specific effect on the magnitude of the peak viscosity depends on the molecular structure of the additive. Hydrocarbons, along with hydrophobic phenols, increase the peak viscosity, while alcohols and simple phenol, decrease it. SAXS and NMR measurements revealed that hydrocarbons are primarily incorporated into the micellar core, and the observed viscosity enhancement is attributed to the suppression of micellar branching. In contrast, molecules possessing an OH-group intercalate between the surfactant headgroups or reside at the micellar surface. For hydrophobic phenols, the ability to form stable hydrogen bonds results in a significant increase in the maximum viscosity. This interaction substantially reduces the salt concentration required to reach peak viscosity; in this case, the micellar charge density remains relatively high, and electrostatic repulsion hinders micellar branching. On the other hand, simple phenols and alcohols decrease viscosity because their higher water solubility allows them to easily redistribute across different regions of the micelle surface, thereby facilitating micellar branching. The dimensionless parameters accounting for the effect of the studied additives on the salt curve characteristics were determined. These parameters were shown to depend on a composite molecular parameter, defined as the ratio of the surfactant volume to the additive volume multiplied by the octanol–water partition coefficient, vBS/vALogP.

Developability assessment facilitates the selection of antibody drug candidates with desirable pharmaceutical properties. However, it remains uncertain whether agitation-induced aggregation can be predicted from standard developability parameters. Here, we investigated whether key biophysical parameters predict agitation-induced aggregation of monoclonal antibodies (mAbs). To this end, we generated a benchmark data set by characterizing the aggregation upon agitation in the presence of an air–liquid interface of ten approved mAbs reformulated in a common surfactant-free buffer. The extent of aggregation varied substantially among mAbs and was primarily dependent on antibody identity. Flow imaging microscopy combined with machine learning revealed micrometre-sized aggregates with distinct morphologies, consistent with aggregation at air–liquid interfaces. Examination of thin liquid films and foams confirmed the presence of aggregates directly at the air–liquid interface and, therefore, the critical role of this interface for antibody aggregation during agitation. We then applied fluorescence-based, light scattering, and chromatographic techniques to determine standard developability parameters for each mAb, including apparent melting temperature (Tm), nonreversibility onset temperature (Tnr), aggregation onset temperature (Tagg), diffusion self-interaction parameter (kD), hydrophobic interaction chromatography retention time, and relative monomer yield after isothermal refolding from chemical denaturants. Notably, none of these parameters correlated with agitation-induced aggregation. Finally, we assessed the surface properties of the mAbs via drop shape analysis and found that the combination of surface pressure and elastic modulus yields a good correlation with the concentration of micrometre-sized aggregates formed due to agitation. Overall, these findings highlight limitations in predicting mAb interfacial stability using standard developability assays and underscore the importance of studying antibody behavior at interfaces.

Molecular dynamics simulations are employed to investigate the crystallization of pentadecane-containing systems. Reference crystalline and rotator phase constructed from crystallographic data benchmark the structures formed upon cooling. Phase identification is achieved through global and local structural descriptors, with the fraction of gauche conformations and angular P₂ profiles outlined as the most sensitive indicators.
Pentadecane exhibits a markedly more stable rotator phase than hexadecane. This is confirmed by simulations spanning more than 30 K for the reference rotator phase. In this temperature range, a model regular rotator phase of pentadecane remains stable without undergoing significant structural changes, showing high reproducibility across independent trajectories. This contrasts hexadecane, for which a rotator phase rapidly transforms toward a triclinic structure [Iliev et al. 2023]. The presence of a surfactant in the system promotes heterogeneous nucleation, shifts crystallization to higher temperatures, and stabilizes the rotator phase, in agreement with experiments.
A computationally efficient protocol for simulating SAXS spectra from MD trajectories is proposed. The simulated spectra align very well with experimental data for both crystalline and rotator phases. Crystallographic lattice parameters can be extracted from the most intense SAXS peaks, even for experimentally unknown structures, demonstrating the general applicability of the approach to solid-state phase analysis.