Sulfur-containing amino acids, Methionine (Met) and Cysteine (Cys), are very susceptible to Reactive Oxygen Species (ROS). Therefore, sulfur-based reactions regulate many biological processes, playing a key role in maintaining cellular redox homeostasis and modulating intracellular signaling cascades. In oxidative conditions, Met acts as a ROS scavenger, through Met sulfoxide formation, while thiol/disulfide interchange reactions take place between Cys residues as a response to many environmental stimuli. In this work, we apply a QM/MM theoretical–computational approach, which combines quantum–mechanical calculations with classical molecular dynamics simulations to estimate the free energy profile for the above-mentioned reactions in solution. The results obtained, in good agreement with experimental data, show the validity of our approach in modeling sulfur-based reactions, enabling us to study these mechanisms in more complex biological systems.

Here we present a theoretical-computational study dealing with the evaluation of the pKa of the Cysteine residues in Thioredoxin (TRX) and in its complex with the Thioredoxin-interacting protein (TXNIP). The free energy differences between the anionic and neutral form of the Cysteine 32 and 35 have been evaluated by means of the Perturbed Matrix Method with classical perturbations due to both the environment and an exogenous electric field as provided by Molecular Dynamics (MD) simulations. The evaluation of the free energies allowed us to show that the effect of the perturbing terms is to lower the pKa of Cysteine 32 and Cysteine 35 with respect to the free amino-acid. On the other hand, in the complex TRX-TXNIP, our data show an enhanced stabilization of the neutral reduced form of Cys 35. These results suggest that external electric stimuli higher than 0.02 V/nm can modulate the Cysteine pKa, which can be connected to the tight regulation of the TRX acting as an antioxidant agent.

Surfactants are very important compounds that are ubiquitous in biological systems and detergents. Among them, ferrocene surfactants are a very valuable class of stimuli-responsive materials since the presence of ferrocene moiety discloses the chance to control and even modify their amphiphilic properties via a redox-induced change in the surfactant charge. In this paper, we report a new ferrocene-based surfactant: a ferrocene C-3 derivative of cholic acid, a non-classical surfactant. The title compound of this work was meant to show the significant self-assembly behaviour typical of bile salts, improved by the presence of the aromatic ferrocene subunit. We intended to demonstrate that the presence of the redox mediator should provide the derivative with sensitivity to an oxidative stimulus and control over the aggregation properties. The title compound was prepared in two steps from easily accessible precursors, and its optical properties were investigated through UV-Vis absorption spectroscopy. The determination of its critical micellar concentration and redox potential confirmed this derivative’s amphiphilic nature and its tendency to be reversibly oxidized.

Porphyrins are versatile aromatic building blocks that act as chiral probes, able to sense and amplify the chiral information given by a proper environment. Their ability to form chiral architectures makes them ideal candidates for designing smart devices for the stereospecific recognition. In this work, bile salts (BS), unconventional chiral surfactant with a peculiar facial amphiphilicity, are used as chiral trigger to induce stereospecific porphyrin aggregation. The BS sodium cholate (NaC) and deoxycholate (NaDC) are used as inductors to drive the chiral aggregation of the achiral 5-(4-carboxyphenyl)-10,15,20-(triphenyl)porphyrin (H2CTPP). Remarkably, varying the H2CTPP/BS molar ratio in buffered aqueous solution, porphyrin self-assembly leads to the formation of fibrillar aggregates that tend to pack in micrometric bundles of fibres. At a 1/100 H2CTPP/BS molar ratio (i.e. BS at 1 mM), these aggregates feature a pronounced supramolecular chirality (𝑔-factor of ca. 0.1) that can be tuned by adjusting the solvent composition. Conversely, at a 1/1000 molar ratio, i.e. above the BS critical micellar concentration, porphyrin remains in its monomeric form inside the hydrophobic core of BS micelles, with no detectable chirality. The chiral self-assembly significantly affects the optical properties in solution (both absorption and emission), revealing the sensitivity of the system to aggregation. Preliminary results show that deposition of the chiral aggregates on quartz surfaces yields solid-state materials that retain chiral properties.