Deciphering Stereoselectivity in Hurd-Claisen Rearrangements: A Comprehensive Study of Electrostatic Interactions from Shubin's Energy Decomposition Analysis.

In this study, we explore the stereoselectivity of Hurd-Claisen Rearrangements, focusing on the influence of two electron-withdrawing groups and eight diverse substituents. Utilizing the Curtin-Hammett principle, we performed energy calculations for reactions, products, and transition states using the M062X/def2TZVPP compound model. Our analysis reveals that kinetic factors predominantly dictate the reaction equilibrium. A key aspect of our research is the application of Shubin's energy decomposition analysis to optimized transition states, highlighting the significant role of electrostatic interactions in determining stereoselectivity. We further dissected each transition state into four fragments: the electron-withdrawing groups ($CO_2Et$, $CN$), the Hurd group ($H$), various substituents ($CH_3$, $Et$, $SProp$, $TBut$, $IsoBut$, $NH_2Ph$, $NO_2Ph$, $Ph$), and the central fragment. This fragmentation approach enabled an in-depth analysis of group dipole moments, providing insights into the electrostatic forces at play. Our findings shed light on the intricate mechanisms driving stereoselectivity in Hurd-Claisen Rearrangements and enhance the understanding of molecular interactions, offering valuable implications for organic synthesis.

α-Alkylidene δ-lactones inhibit quorum sensing phenotypes in Chromobacterium strain CV026 showing interaction with the CviR receptor.

Disruption of bacterial quorum sensing (QS) is presented as a promising strategy to overcome clinically relevant and phytopathogenic bacteria. This work presents α-alkylidene δ-lactones as new chemical scaffolds that inhibit the biosynthesis of violacein in the biosensor strain Chromobacterium CV026. Three molecules displayed higher than 50% violacein reduction when tested at concentrations lower than 625 µM. The most active α-alkylidene δ-lactone inhibited the hydrolysis of chitin concomitantly with the inhibition of violacein production in CV026, suggesting the disruption of its QS machinery. Further, RT-qPCR and competition experiments showed this molecule to be a transcriptional inhibitor of the QS-regulated operon vioABCDE. Docking calculations suggested a good correlation between binding affinity energies and inhibition effects, with all molecules positioned within the CviR autoinducer-binding domain (AIBD). The most active lactone yielded the best binding affinity energy, most probably due to its unprecedented binding with the AIBD. Our results show α-alkylidene δ-lactones as promising chemical scaffolds for the development of new QS inhibitors affecting LuxR/LuxI-systems.

Development and validation of analytical method for identification of new psychoactive substances using linear retention indexes and gas chromatography-mass spectrometry.

New Psychoactive Substances (NPS) are quickly developing to evade legislation, posing unprecedented challenges to public health and law enforcement authorities around the world. The aim of this work was to develop and validate a simple and reliable non-target gas chromatography/mass spectrometry (GC/MS) analytical method based on linear retention indexes for the expeditious identification of NPS without the need of analytical standards. The method was optimized and validated for 22 different drugs covering ten categories: phenethylamines (amphetamine, MDMA, methamphetamine, 25CNBOMe, 2-FA, 5-MAPB), "classic" drugs (cocaine, ephedrine, THC, heroine), synthetic cannabinoids (JWH-081, AM-2201, JWH-210, MAM-2201), piperazines (o-CPP, p-CPP), tryptamines (5-MeO-MiPT), synthetic cathinones (N-ethylpentylone), synthetic opioids (U-47700), aminoindanes (5-IAI), plant-based substances (Salvinorin-A) and "other" (methiopropamine). Three figures of merit (Selectivity, Precision and Robustness) were evaluated with retention index confidence intervals ranging from 0.5 to 20.6 i.u. and relative standard deviations in the range of 0.003% to 0.027% (repeatability) and 0.02% to 0.29% (intermediate precision). A general equation for estimating linear retention index variation as a function of retention time tolerance has been derived. This result in combination with a 2III6-3 fractional factorial design allowed to conclude column polarity to be only statistically relevant factor as compared to gas flow, split ratio, injection temperature, temperature program offset and column brand.

Quantitative 1 H NMR spectroscopy (qNMR) in the early process development of a new quorum sensing inhibitor.

2-methyl-5,6,7,8-tetrahydro-2H-chromen-4(3H)-one (called 6-oxo) is presented as a new AI-1 quorum sensing inhibitor for Vibrio harveyi. The development of a chemical process to afford traceable materials for new biological assays demands the development of analytical methods to ensure their purity and quality. This work describes the use of quantitative 1 H nuclear magnetic resonance (NMR) spectroscopy (qNMR) to assess the purity of a sample of 6-oxo (99.88%) and a sample of its major process impurity (E)-1-(2-hydroxycyclohex-2-en-1-yl)but-2-en-1-one (called HCB; 98.28%). To explore the scope of the use of qNMR to quantify the amount of low-content components in samples related to the chemical process for 6-oxo synthesis, this work also determined the amount of 6-oxo in two HCB samples: (a) the high-purity HCB sample described above and (b) a crude HCB sample collected during the chemical process. Despite the complexity of the crude sample, the amount of 6-oxo was readily assessed and could help to estimate the extent to which 6-oxo was already formed during the HCB synthesis. This information can help the understanding of how the process parameters can be modified to improve the performance of the whole process, by controlling the reaction mechanisms working at each step of this chemical process. In this context, our results reinforce qNMR as a complementary analytical tool for the quantification of the main component found in a sample, contributing to the standardization of reference materials and thus allowing the development of analytical methods for process control and traceability of the samples used for biological assays.

The damselfly genus Mecistogaster (Odonata: Pseudostigmatidae) from the Brazilian Atlantic Forest with a description of three new species and a neotype designation for M. amalia (Burmeister, 1839).

Mecistogaster Rambur, 1842 is a genus of Pseudostigmatidae with five species distributed from Mexico to Argentina. Four of these occur in Brazil, two of which were recorded on the Atlantic Forest, M. amalia (Burmeister, 1839) and M. linearis (Fabricius, 1776). After examining 140 specimens of Mecistogaster amalia it was possible to conclude that it is a complex of species and three new species are described, M. kesselringi sp. nov., M. mielkei sp. nov. and M. nordestina sp. nov. The males differ from each other mainly by the presence or absence of alula, the area occupied by the reddish-brown color of the mesepimeron and penis structure. The females differ mainly by the region occupied for the pale apical area of wing and epiproct shape. The problem of Burmeister's type of M. amalia is discussed and a neotype is erected for it. Distribution and phenology data are provided. A key for males recorded from Brazilian Atlantic Forest is presented.

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides.

Eight new sulfide-based cyclic peptidomimetic analogues of solonamides A and B have been synthesized via solid-phase peptide synthesis and SN2' reaction on a Morita-Baylis-Hillman (MBH) residue introduced at the N-terminal of a tetrapeptide. This last step takes advantage of the electrophilic feature of the MBH residue and represents a new cyclization strategy occurring. The analogues were prepared in moderate overall yields and did not show toxic effects on Staphylococcus aureus growth and were not toxic to human fibroblasts. Two of them inhibited the hemolytic activity of S. aureus, suggesting an interfering action in the bacterial quorum sensing similar to the one already reported for solonamides.

Unprecedented E-stereoselectivity on the sigmatropic Hurd-Claisen rearrangement of Morita-Baylis-Hillman adducts: a joint experimental-theoretical study.

Herein we report the first systematic investigation of the tandem mercury(ii) catalysed transvinylation/Hurd-Claisen rearrangement of MBH adducts derived from alkyl acrylates. This is the first report of E-selectivity for MBH adducts with alkyl side chains and is complementary to the previously reported Johnson-Claisen and Eschenmoser-Claisen rearrangements. The rearrangement products were obtained in good yields and could be readily converted to 2-alkenyl δ-valerolactones. Combined DFT and F-SAPT studies demonstrate that reaction rates are primarily governed by non-covalent interactions dictating the relative stability of the transition states. Our F-SAPT calculations revealed that the hyperconjugative effects are not so significant, but that electrostatic interactions, instead, are the driving forces for the relative E : Z stereoselectivity.

Preparation of terpolymer capsules containing Rosmarinus officinalis essential oil and evaluation of its antifungal activity.

The essential oil from Rosmarinus officinalis presents antifungal activity and is used in industry as a natural preserving agent. However, essential oils are unstable compounds. So, the encapsulation of essential oils is a technique used to protect it, minimizing degradation and reducing undesired interaction with the other formulation components. Thus, this work focuses on the synthesis of terpolymeric capsules containing essential oil from Rosmarinus officinalis, aiming to use it as an antifungal component in cosmetics. The capsules were obtained via terpolymerization of methyl methacrylate, styrene and methacrylic acid in a dispersed phase polymerization process. The properties of the polymers and the fungicide activity were evaluated. The studied essential oil presented a Minimum Inhibitory Concentration (MIC) ranging from 2.25 to 4.5 mg mL-1 and a Minimum Fungicidal Concentration (MFC) from 4.5 to 9.0 mg mL-1 for strains of Candida albicans, Candida glabrata and Candida parapsilosis, and after the encapsulation process, the antifungal activity of the oil was maintained. Additionally, cytotoxicity assays against fibroblast cell lines and human keratinocytes showed that the polymeric nanocapsules containing Rosmarinus officinalis essential oil can be regarded as a very promising material intended for cosmetics and drug delivery applications.

(1R,2S,5R)-5-Methyl-2-[2-(4-nitro-phen-yl)propan-2-yl]cyclo-hexyl 2-(4-meth-oxy-phen-yl)-2,5-di-hydro-1H-pyrrole-1-carboxyl-ate: crystal structure and Hirshfeld analysis.

In the title compound, C28H34N2O5, the adjacent ester and nitro-benzene substituents are connected via an intra-molecular methyl-ene-C-H⋯π(nitrobenzene) inter-action and the mol-ecule approximates to a U-shape. The di-hydro-pyrrole ring (r.m.s. deviation = 0.003 Å) is almost co-planar with the carboxyl-ate residue [Cm-N-C1-Oc (m = methine, c = carbox-yl) torsion angle = 1.8 (4)°] but is orthogonal to the 4-meth-oxy-benzene ring [dihedral angle = 84.34 (17)°]. In the crystal, methyl-ene-C-H⋯O(carbon-yl) inter-actions lead to linear supra-molecular chains along the b-axis direction, which pack without directional inter-actions between them. The analysis of the calculated Hirshfeld surface points to the importance of weak inter-atomic H⋯H, O⋯H/H⋯O and C⋯H/H⋯C contacts in the crystal.

Revalidation of Platystigma Kennedy, 1920, with a synopsis of the quadratum species group and the description of three new species (Odonata: Pseudostigmatidae).

The genus Platystigma Kennedy, 1920 is revalidated based mainly on the third segment of the penis that is plate-like, whereas in the other Pseudostigmatidae it is a flagellum. Dijkstra et al (2014) have merged this family into the Coenagrionidae. However, we prefer to maintain the long-used name Pseudostigmatidae until more detailed phylogenetic studies with more sampling are done. Eight species are here considered in the genus, three of which are described as new: P. humaita, P. minimum and P. quadratum. The genus is divided in two species group, jocaste and quadratum, the latter studied here. The hitherto unknown male of P. martinezi (Machado 1985) is described for the first time. Evidence for exophytic oviposition is presented in at least one species of the genus. A key is provided for the species of the quadratum group.

Exogenous nucleosome-binding molecules: a potential new class of therapeutic drugs.

Constant changes in the structure of chromatin regulate gene expression. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Conceptually, the nucleosome was first identified as a therapeutic target 14 years ago, when small molecules started to be elegantly designed for nucleosomal DNA binding. Concomitantly, emergent drugs that target enzymes that affect chromatin structure have been developed to a treat myriad of diseases, such as cancer. Here, we discuss the development of more complex molecules, such as peptides and peptidomimetics, to directly target the nucleosome surface to modulate chromatin structure. This new strategy presents great challenges that need to be overcome to develop the exogenous nucleosome-binding molecules (eNBMs) as therapeutic agents.

Philogenia nemesioi, a new damselfly from Peru (Odonata, Megapodagrionidae)

Philogenia nemesioi, a new damselfly from Peru (Odonata, Megapodagrionidae). Philogenia nemesioi sp. nov. is described and illustrated based on one male specimen collected on forests of the eastern slope of the Peruvian Andes at 900 m. It belongs to the cristalina group, but differs from other species of the group by the structure of the anal appendage.

"Dba-free" palladium intermediates of the Heck-Matsuda reaction.

The "dba-free" Heck-Matsuda reaction was investigated via direct ESI-MS(/MS) monitoring. Palladium species involved in the reduction of Pd(II) during a Wacker type reaction and several "dba-free" arylpalladium transient complexes were detected and characterized. Based on these findings, a more comprehensible catalytic cycle for this pivotal reaction is suggested.

Carajathemis simone, new genus and species from Brazil (Odonata: Libellulidae).

Carajathemis simone n. gen., n.sp. from the state of Pará, Brazil, is described and illustrated based on 22 specimens collected in a "canga" (laterite) lake within the forest at the Flona de Carajás, Parauapebas Municipality. The new libellulid genus fits in the subfamily Sympetrinae and the male keys out to Erythemis in Garrison et al. (2006). The new taxon has a combination of characters that makes it different from all genera of Sympetrinae including Erythemis. The species is remarkable by its large size, pleural striping and especially by the complex and strongly dimorphic leg armature. It seems to be restricted to shallow, rainfall-dependent, iron-rich lakes.

Lauromacromia bedei sp. nov. from the State of Minas Gerais, Brazil ( Odonata, Corduliidae )

Lauromacromia bedei é descrita e ilustrada com base em um exemplar macho coletado em um rio da região de cerrado do estado de Minas Gerais, Brasil.