Progress in the Understanding of the Key Pharmacophoric Features of the Antimalarial Drug Dihydroartemisinin: An Experimental and Theoretical Charge Density Study

The accurate, experimental charge density distribution, ρ( r ), of the potent antimalarial drug dihydroartemisinin (DHA) has been derived for the first time from single‐crystal X‐ray diffraction data at T=100(2) K. Gas‐phase and solid‐state DFT simulations have also been performed to provide a firm basis of comparison with experimental results. The quantum theory of atoms in molecules (QTAIM) has been employed to analyse the ρ( r ) scalar field, with the aim of classifying and quantifying the key real‐space elements responsible for the known pharmacophoric features of DHA. From the conformational perspective, the bicyclo[3.2.2]nonane system fixes the three‐dimensional arrangement of the 1,2,4‐trioxane bearing the active O? O redox centre. This is the most nucleophilic function in DHA and acts as an important CH???O acceptor. On the contrary, the rest of the molecular backbone is almost neutral, in accordance with the lipophilic character of the compound. Another remarkable feature is the C? O bond length alternation along the O‐C‐O‐C polyether chain, due to correlations between pairs of adjacent C? O bonds. These bonding features have been related with possible reactivity routes of the α‐ and β‐DHA epimers, namely 1) the base‐catalysed hemiacetal breakdown and 2) the peroxide reduction. As a general conclusion, the base‐driven proton transfer has significant non‐local effects on the whole polyether chain, whereas DHA reduction is thermodynamically favourable and invariably leads to a significant weakening (or even breaking) of the O? O bond. The influence of the hemiacetal stereochemistry on the electronic properties of the system has also been considered. Such findings are discussed in the context of the known chemical reactivity of this class of important antimalarial drugs.     

An Automatic Molecular Dispenser of Chloride

The combined activity of the 1.1.1‐cryptand and of a dicopper(II) bistren cryptate complex including chloride makes the Cl^? ion be continuously and slowly delivered to the solution, without any external intervention. The 1.1.1‐cryptand slowly releases OH^? ions, according to a defined kinetics, and each OH^? ion displaces a Cl^? ion from the cryptate. Chloride displacement induces a sharp colour change from bright yellow to aquamarine and can be conveniently monitored spectrophotometrically, even in diluted solutions. The 1.1.1‐cryptand is the motor of a molecular dispenser (the dicopper(II) cryptate) delivering chloride ion automatically, from the inside of the solution.     

Effects of Salts on the Micellization of a Short-Tailed Nonionic Ethoxylated Surfactant: An Intradiffusion Study

In commercial formulations, surfactants are often co-formulated with inorganic electrolytes, which are included as inexpensive thickeners. Salts affect the surfactant’s aggregative and functional behavior. However, while the electrolyte effect on the self-aggregation of ionic surfactants can be rationalized in terms of electrostatic interactions, in the case of nonionic surfactants the molecular determinants are still unclear. In this work, we investigate the effects of alkali and alkaline–earth metal chlorides on the micellization of the nonionic surfactant hexyl penta(oxyethylene) ether, C₆E₅, in aqueous solution. To this aim, the C₆E₅ intradiffusion (also named self-diffusion) coefficient in aqueous mixtures of various alkali and alkaline–earth metal chlorides was measured by pulsed gradient spin-echo NMR. The results show that all the considered electrolytes cause a decrease of the surfactant critical micellar concentration, cmc, while the micellar size is almost unaffected. The experimental evidence can be interpreted in terms of de-hydration of the apolar alkyl tails with a minor contribution arising from the dehydration of the poly(ethylene oxide) headgroups. The order of effectiveness of the different cations follows the Hofmeister series, some aspects of which are briefly discussed.     

Combined Experimental and Multivariate Model Approaches for Glycoalkaloid Quantification in Tomatoes

The intake of tomato glycoalkaloids can exert beneficial effects on human health. For this reason, methods for a rapid quantification of these compounds are required. Most of the methods for α-tomatine and dehydrotomatine quantification are based on chromatographic techniques. However, these techniques require complex and time-consuming sample pre-treatments. In this work, HPLC-ESI-QqQ-MS/MS was used as reference method. Subsequently, multiple linear regression (MLR) and partial least squares regression (PLSR) were employed to create two calibration models for the prediction of the tomatine content from thermogravimetric (TGA) and attenuated total reflectance (ATR) infrared spectroscopy (IR) analyses. These two fast techniques were proven to be suitable and effective in alkaloid quantification (R² = 0.998 and 0.840, respectively), achieving low errors (0.11 and 0.27%, respectively) with the reference technique.     

Many-body interband tunneling as a witness of complex dynamics in the Bose-Hubbard model

A perturbative model is studied for the tunneling of many-particle states from the ground band to the first excited energy band, mimicking Landau-Zener decay for ultracold, spinless atoms in quasi-one-dimensional optical lattices subjected to a tunable tilting force. The distributions of the computed tunneling rates provide an independent and experimentally accessible signature of the regular-chaotic transition in the strongly correlated many-body dynamics of the ground band.     

A variational method for the calculation of spin-rovibronic energy levels of triatomic molecules with three interacting electronic states

A general method is presented for the evaluation of the spin rovibronic energy levels of triatomic molecules with up to three interacting potential energy surfaces. The full theory is outlined in detail, both for singlet and for doublet electronic states and the method is then applied to the benchmark example of C₂H. High quality multireference configuration interaction calculations have been carried out to generate the 3-dimensional near-equilibrium adiabatic potential energy surfaces of the three lowest 1²A'(X²Σ⁺), 2²A'(A²Π), 1²A''(A²Π) electronic states of C₂H, and the pair of interacting states of A 0 symmetry have then been diabatized. Results are presented for J up to 7/2 and compared with gas-phase high resolution experimental results for energies up to 5600 cm¹.