(1) Background: the theoretical modelling of reactions occurring in liquid phase is a research line of primary importance both in theoretical–computational chemistry and in the context of organic and biological chemistry. Here we present the modelling of the kinetics of the hydroxide-promoted hydrolysis of phosphoric diesters. (2) Method: the theoretical–computational procedure involves a hybrid quantum/classical approach based on the perturbed matrix method (PMM) in conjunction with molecular mechanics. (3) Results: the presented study reproduces the experimental data both in the rate constants and in the mechanistic aspects (C–O bond vs. O–P bond reactivity). The study suggests that the basic hydrolysis of phosphodiesters occurs through a concerted $A_N{D}_N$ mechanism, with no formation of penta-coordinated species as reaction intermediates. (4) Conclusions: the presented approach, despite the approximations, is potentially applicable to a large number of bimolecular transformations in solution and therefore leads the way to a fast and general method to predict the rate constants and reactivities/selectivities in complex environments.

Hypothesis: doxorubicin hydrochloride (DX) is a widely used chemotherapeutic agent whose severe side-effects can be attenuated by suitably designing drug delivery systems. With this aim, the complexation between DX and the biocompatible and biodegradable sodium alginate (ALG) is here proposed for DX encapsulation.Experiments: the synergistic interaction in water between DX and ALG led to the self-assembly of DX@ALG nanoparticles that have been characterized by several spectroscopic techniques, dynamic light scattering (DLS), atomic force microscopy (AFM) and quantum mechanics (QM) calculation. A preliminary survey of the in-vitro cell toxicity of DX@ALG is also reportedFindings: DX@ALG complexes formation result in the quenching of DX that shows chiroptical properties characteristic of supramolecular gels of DX. The association of DX and alginate into supramolecular nanoparticles takes place at low DX concentration and without salt addition. More than 80 % of DX complexed with alginate is forming a gel like phase, and complexes show a high DX load. Nanoparticle formation is revealed by DLS and AFM. QM calculations support the formation of supramolecular DX aggregates by π-π stacking and hydrogen bonds.