Commercially available pesticides were examined as Mus musculus and Homo sapiens acetylcholinesterase (mAChE and hAChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards, molecular docking and dynamics SB studies were performed on either mAChE or hAChE, to predict the listed pesticides’ binding modes. Calculated energies of global minima (E_{glob_min}) and free energies of binding (∆G_binding) were correlated with the pesticides’ acute toxicities (i.e., the LD₅₀ values) against mice, as well to generate the model that could predict the LD₅₀s against humans. Although for most of the pesticides the low E_{glob_min} correlates with the high acute toxicity, it is the ∆G_binding that conditions the LD₅₀ values for all the evaluated pesticides. Derived pLD₅₀ = f(∆G_binding) mAChE model may predict the pLD₅₀ against hAChE, too. The hAChE inhibition by atrazine, propazine, and simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM) DFT mechanistic and concentration-dependent kinetic studies, enriching the knowledge for design of less toxic pesticides.

Vanillic acid is used in the food industry and perfumery, and the optimization of its extraction process from the natural source is important for saving time and money. The presence of vanillic acid in pumpkin seeds was proven using HPLC analysis. Computational optimization of the extraction shows that for the concentration of ethanol 40% and solmodul: V/m=20, the optimum condition for the extraction of vanillic acid from pumpkin seeds was 100 min and 450C. The estimation of fitting for each kinetic model to the experimental kinetic data was performed using the root mean square, standard deviation, and the correlation coefficient. Ponomarev model was shown as the most suitable with the highest accuracy among the six considered kinetic models. The enthalpy and entropy changes were positive, while the Gibbs free energy was negative and decreased when temperature increased during the thermodynamic analysis. Therefore, the extraction of vanillic acid from pumpkin seeds was endothermic, spontaneous, and irreversible.

The study was designed to examine the influence of solvent concentration (ethanol/water 20-80% by volume), extraction time (15-240 min) and extraction technique on the extraction yield of phenolic compounds, flavonoids and antioxidant activity from Morus nigra L., Morus rubra L. and Morus alba L. fruits. The optimum conditions for the extraction of total phenols, flavonoids and monomeric anthocyanins by the maceration and ultrasonic extraction processes were: 213.6 min with 80% ethanol, and 182.1 min and 71.2% ethanol, respectively (black mulberry), and 216.5 min with 78.3% ethanol and 198.7 min and 70.6% ethanol, respectively (red mulberry). In case of white mulberry for the extraction of total phenols and flavonoids optimum extraction conditions (maceration and ultrasonic) were 232.7 min and 80% ethanol, and 187.2 min and 68.7% ethanol, respectively (white mulberry). Obviously, ultrasonic extraction was less time consuming, and it requires for all performed extractions solvent with less percentage of ethanol. ********* In press - Online First. Article has been peer reviewed, accepted for publication and published online without pagination. It will receive pagination when the issue will be ready for publishing as a complete number (Volume 47, Issue 3, 2019). The article is searchable and citable by Digital Object Identifier (DOI). DOI link will become active after the article will be included in the complete issue. *********

2-O-tert-Butyldimethylsilyl-4,6-bis-O-pyrenoyl-myo-inositol-1,3,5-orthoformate (6) and 2-O-tert-butyldimethylsilyl-4-O-[4-(dimethylamino)benzoyl]-6-O-pyrenoyl-myo-inositol-1,3,5-orthoacetate (10) adopt conformationally restricted unstable chairs with five axial substituents. In the symmetrical diester 6, the two π-stacked pyrenoyl groups are electron acceptor–donor partners, giving a strong intramolecular excimer emission. In the mixed ester 10, the pyrenoyl group is the electron acceptor and the 4-(dimethylamino)benzoyl ester is the electron donor, giving a strong intramolecular exciplex emission. The conformation of the mixed ester 10 was assessed using ¹H NMR spectroscopy (¹H-NOESY) and computational studies. which showed the minimum inter-centroid distance between the two aromatic systems to be ∼3.9 Å. Upon addition of acid, the orthoformate/orthoacetate trigger in 6and 10 was cleaved, which caused a switch of the conformation of the myo-inositol ring to the more stable penta-equatorial chair, leading to separation of the aromatic ester groups and loss of excimer and exciplex fluorescence, respectively. This study provides proof of principle for the development of novel fluorescent molecular probes.