Co-Crystals of Resveratrol and Polydatin with L-Proline: Crystal Structures, Dissolution Properties, and In Vitro Cytotoxicities.

Resveratrol (RSV) and polydatin (PD) have been widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, and diabetes, among several others. However, their low solubility hinders their further applications. In this work, we show that the solubility of PD can be boosted via its co-crystallization with L-proline (L-Pro). Two different phases of co-crystals, namely the RSV-L-Pro (RSV:L-Pro = 1:2) and PD-L-Pro (PD:L-Pro = 1: 3), have been prepared and characterized. As compared to the pristine RSV and PD, the solubility and dissolution rates of PD-L-Pro in water (pH 7.0) exhibited a 15.8% increase, whereas those of RSV-L-Pro exhibited a 13.8% decrease. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine RSV, PD, RSV-L-Pro, and PD-L-Pro against lung cancer cell line A549 and human embryonic kidney cell line HEK-293 indicated that both compounds showed obvious cytotoxicity against A549, but significantly reduced cytotoxicity against HEK-293, with PD/PD-L-Pro further exhibiting better biological safety than that of RSV/RSV-L-Pro. This work demonstrated that the readily available and biocompatible L-Pro can be a promising adjuvant to optimize the physical and chemical properties of RSV and PD to improve their pharmacokinetics.

Theoretical Study of Ruthenium(0)-Catalyzed Transfer Hydrogenative Cycloaddition of Cyclohexadiene and Norbornadiene with 1,2-Diols to Form Bridged Carbocycles.

The recent success of Krische et al. ( Angew. Chem., Int. Ed. 2017 , 56 , 14667 -14671 ) in achieving a ruthenium(0)-catalyzed transfer hydrogenative cycloaddition of 1,2-diols with cyclohexadiene and norbornadiene in excellent yield with exo- and diastereoselectivity represents an exciting development in the synthesis of bridged carbocycles. In the present work, the possible catalytic mechanisms and origin of the exo- and diastereoselectivity for cyclohexadiene and norbornadiene were studied in detail by density functional theory calculations. The theoretical results indicate that the exoselective pathway for the cyclohexadiene substrate proceeds by a novel two-step successive C-C coupling, while the endoselective pathway undergoes the C-C coupling reaction in a conventional concerted manner. The origin of the preferential chemoselectivity of dione-cyclohexadiene C-C coupling over aromatization to benzene was investigated. Aromatization to benzene is unfavorable because of the large distortion energy of the three-membered ring in the transition state of hydrogen migration. From distortion/interaction analysis, for norbornadiene, the distortion energy plays the main role in determining the exoselectivity.

The mechanism and origin of the regioselectivity of cobalt-catalyzed annulation of allenes with benzamide: a computational study.

Thrimurtulu et al. recently reported unprecedented cobalt-catalyzed annulation of allenes with benzamide (N. Thrimurtulu, A. Dey, D. Maiti, C. M. R. Volla, Angew. Chem., Int. Ed., 2016, 55, 12361-12365). In this reaction, the substituent on the allene controls the regioselectivity for the formation of either dihydroisoquinolin-1(2H)-one or isoquinolin-1(2H)-one. In the present study, density functional theory calculations were performed to investigate the detailed reaction mechanism and the origin of the experimentally observed regioselectivity. A systematic search shows that the electronic and steric effects of the substituent on the allene determine which of the two allene insertions is followed, and thus determine the regioselectivity. The bulky diphenylphosphonate and two phenyl substituents of the allenylphosphonate and diarylallene favor C1[double bond, length as m-dash]C2 insertion, which eventually leads to the formation of isoquinolin-1(2H)-one. In contrast, for the arylallene, which has a relatively electron-rich C2[double bond, length as m-dash]C3 bond, C2[double bond, length as m-dash]C3 insertion is favored and eventually leads to the formation of dihydroisoquinolin-1(2H)-one. The calculations also explain why annulation rather than hydroarylation of benzamide with allenylphosphonate occurs with a cobalt catalyst.

Mechanism of Iridium-Mediated Selective Arene Cleavage: Insights from Density Functional Theory (DFT) Calculations.

The mechanism and regioselectivity of iridium-mediated cleavage of aromatic C-C bonds in a series of monomethylated, dimethylated, and trimethylated benzenes without the activation of weaker C-H and C-C bonds are clarified using density functional theory (DFT) calculations. The calculations explained why the reactivity of the coordinated arene in the observed C-C bond cleavage reaction decreases as the degree of substitution decreases.