Elucidation of the atroposelectivity in the synthesis of axially chiral thiohydantoin derivatives.

Recently, Sarigul and Dogan have synthesized a number of enantiomerically enriched axially chiral atropoisomeric 2-thiohydantoins by the reaction of l-amino acid ester salts and o-aryl isothiocyanates in the presence of triethyl amine (TEA) in dichloromethane. The non-axially chiral derivative 5-methyl-3-phenyl-2-thiohydantoin gave a racemic product whereas the axially chiral 5-methyl-3-o-bromophenyl-2-thiohydantoin was less prone to racemize at C5 of the heterocyclic ring. In this study, we present a computational study (M06-2X/6-311+G(d,p) for C, H, O, N and S; M06-2X/6-311++G(3df,3pd) for Br) in order to propose plausible mechanisms for the racemization and cyclization steps for 2-thiohydantoin derivatives. The study includes rationalization based on steric as well as the electrostatic effects to elucidate the epimerization differences at C5.

Stimuli-responsive poly(hydroxyethyl methacrylate) hydrogels from carboxylic acid-functionalized crosslinkers.

Tailoring hydrogel properties by modifications of the crosslinker structure is a good method for the design of hydrogels with a wide range of properties. In this study, two novel carboxylic acid-functionalized dimethacrylate crosslinkers (1a and 2a) are synthesized by the reaction of poly(ethylene glycol) or 2-hydroxyethyl disulfide with tert-butyl α-bromomethacrylate followed by cleavage of tert-butyl groups using trifluoroacetic acid. Their copolymerization reactivity with 2-hydroxyethyl methacrylate (HEMA) investigated by photopolymerization studies performed on photo-differential scanning calorimetry shows higher reactivity of 2a compared to 1a. These crosslinkers are then used at different ratios for fabrication of pH- and redox-responsive poly(2-hydroxyethyl methacrylate)-based hydrogels. The swelling behavior of the hydrogels is found to be dependent on the structure of the crosslinker, degree of crosslinking, pH, and CaCl2 concentration. The redox-responsive behavior is demonstrated by degradation of the hydrogel upon exposure to 1,4-dithiothreitol. The dye Rhodamine 6G and the drug resorcinol are used as models to demonstrate the pH and redox dependent release of loaded compounds from the hydrogels. The electrostatic interactions between the carboxylate groups and the positively charged R6G are found to govern the release profile in DTT and counteract the diffusion of dye molecules and significant amount of release (79% in 120 hr) occurs only at highly acidic conditions. The degradation mediated release in DTT is observed better in case of resorcinol (around 88% in 5 hr). Overall, these hydrogels can be regarded as good candidates for several applications, such as matrices for controlled release, tissue repair, and regeneration.

Hydroxyl radical-mediated degradation of diclofenac revisited: a computational approach to assessment of reaction mechanisms and by-products.

Advanced oxidation processes (AOPs) are based on the in situ production of hydroxyl radicals (•OH) and reactive oxygen species (ROS) in water upon irradiation of the sample by UV light, ultrasound, electromagnetic radiation, and/or the addition of ozone or a semiconductor. Diclofenac (DCF), one of the emerging organic contaminants (EOC), is of environmental concern due to its abundancy in water and is known to be subjected to AOPs. The current study uses density functional theory (DFT) to elucidate the mechanisms of the reactions between •OH and DCF leading to degradation by-products, P1-P9. The initial encounter of DCF with •OH is proposed to lead to either the abstraction of a hydrogen or the addition of the hydroxyl radical to the molecule. The results showed that OH addition radicals (R add) are both kinetically and thermodynamically favored over H abstraction radicals (R abs). The intermediate radicals give degradation by-products by subsequent reactions. The by-products P7 and P8 are easily formed in agreement with experimental findings. Finally, acute toxicities at three trophic levels are estimated with the Ecological Structure Activity Relationships program. DCF and most of the by-products were found to be harmful to aquatic organisms, P9 being the only by-product that is not harmful at all three trophic levels.

1,3-Dipolar Cycloaddition Reactions of Low-Valent Rhodium and Iridium Complexes with Arylnitrile N-Oxides.

The reactions between low-valent Rh(I) and Ir(I) metal-carbonyl complexes and arylnitrile oxides possess the electronic and structural features of 1,3-dipolar cycloadditions. Density functional theory (DFT) calculations on these reactions, involving both cyclopentadienyl and carboranyl ligands on the metal carbonyl, explain the ease of the chemical processes and the stabilities of the resulting metallaisoxazolin-5-ones. The metal-carbonyl bond has partial double bond character according to the Wiberg index calculated through NBO analysis, and so the reaction can be considered a normal 1,3-dipolar cycloaddition involving M═C bonds. The rates of formation of the metallacycloadducts are controlled by distortion energy, analogous to their organic counterparts. The superior ability of anionic Ir complexes to share their electron density and accommodate higher oxidation states explains their calculated higher reactivity toward cycloaddition, as compared to Rh analogues.

The origin of exo-stereoselectivity of norbornene in hetero Diels-Alder reactions.

In this study the exo selectivity in the hetero Diels-Alder reaction of atropisomeric 5-benzylidine-2-arylimino-3-aryl-thiazolidine-4-thiones with norbornene was investigated with computational tools. Taking into account the M/P chiral character of the o-methoxyphenyl substituted heterodienes in addition to the exo/endo selectivity, 8 different transition structures were located. Based on the direction of approach of the diene and the dienophile for each plausible path it is found that endo products are not preferred because of the large distortion of norbornene and the rather eclipsed conformations of these transition state structures. Computational results are consistent with the experimental exo/endo selectivity. The computational methodology (M06-2X/6-31+G(d)//B3LYP/6-31+G(d)) was justified by comparison of the experimental rotational barriers with the calculated ones for selected compounds.