Three-Dimensional Fully pi-Conjugated Macrocycles: When Truly 3D-Aromatic and when 2D-Aromatic-in-3D?

Recently, several fully pi-conjugated macrocycles with strongly puckered or cage-type structures have been synthesized and found to exhibit aromatic character according to both experiments and computations. Herein, we examine their electronic structures and put them in relation to truly 3D-aromatic molecules (e.g., closo-boranes and certain charged fullerenes) as well as 2D-aromatic polycyclic aromatic hydrocarbons. We use qualitative theory combined with quantum chemical calculations, and find that the macrocycles explored thus far should be described as 2D-aromatic with three-dimensional structures (abbr. 2D-aromatic-in-3D) instead of truly 3D-aromatic. Besides fulfilling the 6n + 2 pi-electron rule, 3D-aromatic molecules with highly symmetric structures (e.g., Td and Oh) have a number of molecular orbital (MO) levels that are (at least) triply degenerate. At lower symmetries, the triple (or higher) orbital degeneracies should be kept in approximate sense. This last criterion is not fulfilled by macrocyclic cage molecules that are 2D-aromatic-in-3D. Their aromaticity results from a fulfillment of Hückel’s 4n + 2 rule for each individual macrocyclic path, yet, their pi-electron counts are coincidentally 6n + 2 numbers for macrocycles with three tethers of equal lengths. We instead link the 3D-macrocyclic molecules explored earlier to naphthalene, motivating their description as 2D-aromatics albeit with 3D structures. It is notable that macrocyclic cages which are 2D-aromatic-in-3D can be aromatic also when the tethers are of different lengths, i.e., when their pi-electron counts differ from 6n + 2. Finally, we identify tetrahedral and cubic pi-conjugated molecules that fulfill the 6n + 2 rule and which exhibit significant electron delocalization. Yet, their properties are similar to those of analogous compounds with electron counts that differ from 6n + 2. Thus, despite that these tetrahedral and cubic molecules show substantial pi-electron delocalization they should not be classified as true 3D-aromatics.

A Review on Heteroaryl Substituted Pyrazolines with their Pharmacological Activity and SAR Studies

In step with the development of organic chemistry, heterocyclic compounds play an important part. Electron-rich nitrogen containing heterocyclic compounds and their derivatives play key role in diverse biological activities. The wide-ranging functionality and stereochemical complexity in a five-member ring structure is shown by the pyrazole nucleus, which has two nitrogen atoms and exhibit aromatic character. The medicinal chemists have been using the relationship between chemical structure and biological activity of a molecule in drug discovery as the driving force to guide synthetic efforts, to design new chemical derivatives. It has been reported that pyrazoline derivatives possess a broad spectrum of biological activities such as antibacterial, antimicrobial, anti-inflammatory, antioxidant, antidiabetic, anticancer, antifungal, antitubercular, antidepressant, anticonvulsant and analgesic activities. They also possess some potent receptor selective biological activities like monoamine oxidases (MAOs) inhibitor, Nitric oxide synthase (NOS) inhibitor, Angiotensin converting enzyme (ACE) inhibitor, cholecystokinin-1 receptor antagonist and estrogen receptor (ER) ligand activity. Hence in this article, we focus on the pyrazole derivatives having heteroaryl substituents and their pharmacological activities along with their structure–activity relationships in order to create opportunities to explore the full potential of these compounds. Keywords: Heterocyclic compounds, Pyrazolines, Claisen-Schmidt condensation, Chalcone.

Chemical analysis of some Ocimum basilicum medicinal teas

Objectives. Ocimum basilicum is one of the widespread medicinal plants, widely used due to its multiple therapeutic properties (antimicrobial, antiviral, hypoglycemic, antispasmodic, anti-inflammatory, carminative, stomachic, antioxidant, analgesic, etc.), as well as its specific aromatic character. The aim of this study was to comparatively investigate the chemical composition (flavonoids, caffeic acid derivatives, tannins, essential oil) of the aerial parts of some Romanian medicinal teas of Ocimum basilicum. Materials and methods. The content of flavonoids, phenolic acids and tannins in three samples of O. basilicum tea were determined spectrophotometrically. Identification of important phenolic compounds (rutin, isoquercitrin chlorogenic acid and caffeic acid) was performed by thin layer chromatography (TLC). The essential oils were obtained by hydrodistillation method. Outcomes and conclusions. Following the quantitative determinations performed, it can be seen that the basil samples are rich in active principles, and their use for the treatment of some diseases can be justified.

Analysis of Local and Global Aromaticity in Si3C5 and Si4C8 Clusters. Aromatic Species Containing Planar Tetracoordinate Carbon

The minimum energy structures of the Si3C5 and Si4C8 clusters are planar and contain planar tetracoordinate carbons (ptCs). These species have been classified, qualitatively, as global (π) and local (σ) aromatics according to the adaptive natural density partitioning (AdNDP) method, which is an orbital localization method. This work evaluates these species’ aromaticity, focusing on confirming and quantifying their global and local aromatic character. For this purpose, we use an orbital localization method based on the partitioning of the molecular space according to the topology of the electronic localization function (LOC-ELF). In addition, the magnetically induced current density is analyzed. The LOC-ELF-based analysis coincides with the AdNDP study (double aromaticity, global, and local). Moreover, the current density analysis detects global and local ring currents. The strength of the global and local current circuit is significant, involving 4n + 2 π- and σ-electrons, respectively. The latter implicates the Si-ptC-Si fragment, which would be related to the 3c-2e σ-bond detected by the orbital localization methods in this fragment.

Magnetic Aromaticity of Cycloporphyrin Nanorings

The ascertainment of magnetic aromaticity is not necessarily straightforward, especially for large and bent systems, such as the cycloporphyrin nanorings recently synthesized by the group of Anderson. Six of these cycloporphyrin nanorings were studied here computationally. Indirect methods, based on nuclear shielding and magnetizabilities, and direct methods, based on standard quantum mechanics, were both used effectively to determine their magnetically induced current strength, which mostly confirmed Anderson’s classification. However, in the case of hexanions, and in particular for cyclohexaporphyrin hexacations, a significant cancellation of delocalized diatropic and paratropic flow occurred, showing that the resultant faint aromatic character was a result of competing aromatic and antiaromatic contributions, as also evidenced by the ipsocentric method. A warning is renewed on the use of isotropic shielding to determine the tropicity of the magnetically induced current.

Analysis of Local and Global Aromaticity in Si3C5 and Si4C8 Clusters. Aromatic Species Containing Planar Tetracoordinate Carbon

The minimum energy structures of the Si3C5 and Si4C8 clusters are planar and contain planar tetracoordinate carbons (ptCs). These species have been classified, qualitatively, as global () and local () aromatics according to the adaptive natural density partitioning (AdNDP) method, which is an orbital localization method. This work evaluates these species' aromaticity, focusing on confirming and quantifying their global and local aromatic character. For this purpose, we use an orbital localization method based on the partitioning of the molecular space according to the topology of the electronic localization function (LOC-ELF). In addition, the magnetically induced current density is analyzed. The LOC-ELF-based analysis coincides with the AdNDP study (double aromaticity, global and local). Besides, the current density analysis detects global and local ring currents. The strength of the global and local current circuit is significant, involving 4n+2 - and -electrons, respectively. The latter implicates the Si-ptC-Si fragment, which would be related to the 3c-2e -bond detected by the orbital localization methods in this fragment.

Cationic Peptidomimetic Amphiphiles Having a N-Aryl- or N-Naphthyl-1,2,3-Triazole Core Structure Targeting Clostridioides (Clostridium) difficile: Synthesis, Antibacterial Evaluation and an In Vivo C. difficile Infection Model

Clostridioides (also known as Clostridium) difficile is a Gram-positive anaerobic, spore producing bacterial pathogen that causes severe gastrointestinal infection in humans. The current chemotherapeutic options are inadequate, expensive, and limited, and thus inexpensive drug treatments for C. difficile infection (CDI) with improved efficacy and specificity are urgently needed. To improve the solubility of our cationic amphiphilic 1,1′-binaphthylpeptidomimetics developed earlier that showed promise in an in vivo murine CDI model we have synthesized related compounds with an N-arytriazole or N-naphthyltriazole moiety instead of the 1,1′-biphenyl or 1,1′-binaphthyl moiety. This modification was made to increase the polarity and thus water solubility of the overall peptidomimetics, while maintaining the aromatic character. The dicationic N-naphthyltriazole derivative 40 was identified as a C. difficile-selective antibacterial with MIC values of 8 µg/mL against C. difficile strains ATCC 700057 and 132 (both ribotype 027). This compound displayed increased water solubility and reduced hemolytic activity (32 µg/mL) in an in vitro hemolysis assay and reduced cytotoxicity (CC50 32 µg/mL against HEK293 cells) relative to lead compound 2. Compound 40 exhibited mild efficacy (with 80% survival observed after 24 h compared to the DMSO control of 40%) in an in vivo murine model of C. difficile infection by reducing the severity and slowing the onset of disease.

The Determination of Aromatic Character of Several Local Rice Varieties using Phenotypic Analysis and Molecular DNA

The pandan scent in aromatic rice has been known as the result of 8 bp deletions and 3 Single Nucleotide Polymorphisms (SNPS) in BADH2 gene, which produce non-functional betaine aldehyde dehydrogenase (BADH) enzyme. Several DNA markers for aromatic character based on mutation in BADH2 gene have been developed. In our experiment, we analysed the presence of aromatic character in four local rice variety such as Merah Wangi, Pendok, Genjah Arum, and Mentik Wangi Susu using KOH method and DNA molecular method using three DNA markers to detect mutation that responsible for the development of aromatic character. Phenotype analysis using KOH method showed that Merah Wangi, Genjah Arum, and Mentik Wangi Susu produce pandan scents. PCR analysis using Bradbury and Badex7-5, and RM223 markers showed the presence of BADH2 mutation in Merah Wangi and Mentik Wangi Susu, whereas Pendok and Genjah Arum did not show BADH2 mutation using those used three markers. Our results indicate that among four investigated local rice, only Merah Wangi and Mentik Wangi Susu are categorized as aromatic rice whereas Pendok and Genjah Arum are non-aromatic.Keywords: genetic analysis, aromatic rice, specific markers, genetic mutation.