Synthesis of Benzo[4,5]thiazolo[2,3-c][1,2,4]triazole Derivatives via C-H Bond Functionalization of Disulfide Intermediates

Many nitrogen- and sulfur-containing heterocyclic compounds exhibit biological activity. Among these heterocycles are benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles for which two main synthetic approaches exist. Here we report a new synthetic protocol that allows the preparation of these tricyclic compounds via the oxidation of a mercaptophenyl moiety to its corresponding disulfide. Subsequent C-H bond functionalization is thought to enable an intramolecular ring closure, thus forming the desired benzo[4,5]thiazolo[2,3-c][1,2,4]triazole. This method combines a high functional group tolerance with short reaction times and good to excellent yields.     

Recovery of Bioactive Ellagitannins by Ultrasound/Microwave-Assisted Extraction from Mexican Rambutan Peel (Nephelium lappaceum L.)

Rambutan (Nephelium lappaceum L.) is a tropical fruit from Asia which has become the main target of many studies involving polyphenolic analysis. Mexico produces over 8 million tons per year of rambutan, generating a huge amount of agro-industrial waste since only the pulp is used and the peel, which comprises around 45% of the fruit’s weight, is left behind. This waste can later be used in the recovery of polyphenolic fractions. In this work, emerging technologies such as microwave, ultrasound, and the hybridization of both were tested in the extraction of phenolic compounds from Mexican rambutan peel. The results show that the hybrid technology extraction yielded the highest polyphenolic content (176.38 mg GAE/g of dry rambutan peel). The HPLC/MS/ESI analysis revealed three majoritarian compounds: geraniin, corilagin, and ellagic acid. These compounds explain the excellent results for the biological assays, namely antioxidant activity evaluated by the DPPH, ABTS, and LOI (Lipid oxidation inhibition) assays that exhibited great antioxidant capacity with IC₅₀ values of 0.098, 0.335, and 0.034 mg/mL respectively, as well as prebiotic activity demonstrated by a µMax (maximum growth) of 0.203 for Lactobacillus paracasei. Lastly, these compounds have shown no hemolytic activity, opening the door for the elaboration of different products in the food, cosmetic, and pharmaceutical industries.     

Asymptotic singular behaviour of inhomogeneous cosmologies in Einstein-Maxwell-dilaton-axion theory

We present the study of exact inhomogeneous cosmological solutions to a four-dimensional low energy limit of string theory containing non-minimal interacting electromagnetic, dilaton and axion fields. We focus at Einstein-Rosen solutions of Einstein-Maxwell-dilaton-axion equations. Several cases are analyzed and some of them have asymptotically velocity-term dominated (AVTD) singularities.     

Bio-Organometallic Derivatives of Antibacterial Drugs

Overuse and misuse of antibacterial drugs has resulted in bacteria resistance and in an increase in mortality rates due to bacterial infections. Therefore, there is an imperative necessity of new antibacterial drugs. Bio-organometallic derivatives of antibacterial agents offer an opportunity to discover new active antibacterial drugs. These compounds are well-characterized products and, in several examples, their antibacterial activities have been studied. Both inhibition of the antibacterial activity and strong increase in the antibiotic activity of the parent drug have been found. The synthesis of the main classes of bio-organometallic derivatives of these drugs, as well as examples of the use of structure–activity relation (SAR) studies to increase the activity and to understand the mode of action of bio-organometallic antimicrobial peptides (BOAMPs) and platensimicyn bio-organometallic mimics is presented in this article.     

Development of a Neutral Diketopyrrolopyrrole Phosphine Oxide for the Selective Bioimaging of Mitochondria at the Nanomolar Level

Development of novel bioimaging materials that exhibit organelle specific accumulation continues to be at the forefront of research interests and efforts. Among the various subcellular organelles, mitochondria, which are found in the cytoplasm of eukaryotic cells, are of particular interest in relation to their vital function. To date, most molecular probes that target mitochondria utilise delocalised lipophilic cations such as triphenylphosphonium and pyridinium. However, the use of such charged motifs is known to be detrimental to the working function of the mitochondrial transmembrane potential and there remains a strong case for development of neutral mitochondrial fluorescent probes. Herein, we demonstrate for the first time the exploitation of diketopyrrolopyrrole-based chemistries for the realisation of a neutral fluorescent probe that exhibits organelle specific accumulation within the mitochondria at the nanomolar level. The synthesised probe, which bears a neutral triphenylphosphine oxide moiety, exhibits a large Stokes shift and high fluorescence quantum yield in water, both highly sought-after properties in the development of bioimaging agents. In vitro studies reveal no interference with cell metabolism when tested for the human MCF7 breast cancer cell and nanomolar subcellular organelle colocalisation with commercially available mitochondrial staining agent Mitotracker Red. In light of its novelty, neutral structure and the preferential accumulation at nanomolar concentrations we anticipate this work to be of significant interest for the increasingly larger community devoted to the realisation of neutral mitochondrial selective systems and more widely to those engaged in the rational development of superior organic architectures in the biological field.     

About contingent epiderivatives

In this paper we analyze some questions concerning the contingent epiderivative. When the ordering cone is not necessarily pointed we introduce the notion of family of contingent epiderivatives. We also investigate the relationship between the contingent derivative and the generalized epiderivative. Furthermore, we give existence theorems with respect to Daniell cones. As a particular case, we study set-valued maps that take values in Rn.