Organics doi: 10.3390/org7020015

Authors: Tiba M. Hameed Rafid M. Hashim S. J. Abed Raneen Hashim Ridha O. Al-Mohammed Baqer

A new series of eight novel etodolac-based 1,3,4-oxadiazoles was synthesized, characterized, and tested in silico in multidimensional routes, starting with etodolac, a well-known nonsteroidal anti-inflammatory medication (NSAID). In silico studies were performed prior to synthesis using the molecular docking technique in CCDC GOLD suite software (2025.3) to assess the interactions with two key targets involved in cancer pathogenesis: the crystal structure of the epidermal growth factor receptor EGFR tyrosine kinase domain (PDB ID: 4HJO) and the matrix metalloproteinase (MMP-9) complex (PDB ID: 5CUH). ADME studies were performed to assess the physicochemical properties of the synthesized molecules. Importantly, biotransformation prediction also indicated that the derivatives possess high metabolic stability, with hydroxylation of the thio-ether group as the primary predicted biotransformation route. All compounds were characterized using melting point, FT-IR, 1H-NMR, and 13C-NMR spectroscopy. In vitro and/or in vivo experiments are needed to confirm this preliminary anticancer study.

Organics doi: 10.3390/org7010014

Authors: Fabiola Hernández-García Emanuel Pérez-Martínez Raúl Colorado-Peralta Jesús Antonio Cruz-Navarro David Morales-Morales

Salophen-type Schiff base ligands derived from salicylaldehyde and naphthalene aldehydes were synthesized and coordinated to Ni(II) to obtain three nickel complexes (NiL1–NiL3), which were evaluated as heterogeneous electrocatalysts for the methanol electro-oxidation reaction (MOR) in alkaline media. The ligands and complexes were fully characterized by FT-IR, 1H NMR, EPR, DART-MS, and elemental analysis, confirming tetradentate coordination through imine nitrogen and phenoxide oxygen donors. Electrochemical studies were carried out using carbon paste electrodes modified with 15 wt % of each complex. Cyclic voltammetry revealed that the electrocatalytic activity is mediated by the Ni(II)/Ni(III) redox couple, with Ni(III) oxohydroxide species acting as the active sites for methanol oxidation. Among the evaluated systems, NiL1@CPE showed superior performance at low methanol concentrations, while NiL2@CPE and NiL3@CPE exhibited higher current densities at elevated methanol concentrations. Scan-rate studies indicated that the oxidation process is diffusion-controlled, and a linear response to methanol concentration was observed over a wide concentration range. The results demonstrate that ligand structure and coordination geometry play a crucial role in modulating the electrocatalytic behavior of Ni(II) Schiff base complexes, highlighting their potential as cost-effective molecular catalysts for alkaline methanol oxidation.

Organics doi: 10.3390/org7010013

Authors: Lucia Emanuele Rocco Racioppi Maurizio D’Auria

The study aimed to verify the possible use of DFT calculation in the prediction of the orientation in electrophilic aromatic substitution. An activated ortho/para orienting substrate, and a deactivated meta orienting substrate, were used in DFT calculations using B3LYP, B3PW91, BPV86, CAM-B3LP, HCTH, HSEH1PBE, LSDA, MPW1PW91, PBEPBE, TPSSTPSS, and WB97XD functionals. The results showed that the reactivity of anisole can be adequately described considering charge control in reaction performed in hard conditions (nitration), while frontier orbital control can play a role in reactions performed in softer conditions (chlorination). Nitration of benzaldehyde can be rationalized through Hirshfeld charges analysis. Neither the frontier orbital nor Mulliken charges approach adequately account for behavior observed in chlorination of benzaldehyde. The effect of different basis sets was tested performing calculations with B3LYP functional and aug-cc-pVDZ, 6-311G+(d,p), aug-cc-pVQZ, DGTZVP, and LanL2DZ basis sets. For anisole, all basis sets provided a HOMO electron density distribution consistent with experimental reactivity; Hirshfeld charges analysis consistently reproduced the observed reactivity of anisole across all tested basis sets. All the basis sets were able to explain the observed reactivity of benzaldehyde in hard experimental condition, while they failed to give a correct description when a softer reagent was used.

Organics doi: 10.3390/org7010012

Authors: Augusto Rivera Álvaro Castillo Jaime Ríos-Motta Diego Quiroga

In the present work, we describe the synthesis of a new heterocyclic derivative, 2-(naphthalen-1-yl)-2,3,5,6-tetrahydro-1H-isoquinolino[8,1,2-hij]quinazoline 1, using the reaction between the aminal 1,3,6,8-tetraazatricyclo[4.4.1.13,8]dodecane 2 (TATD) and 1-naphthylamine 3 as the first scaffold of a four-step linear synthetic route. In the first step, a condensation catalyzed by acetic acid in 96% ethanol was carried out, leading to the formation of the intermediate 3-(naphthalen-1-yl)-1,2,3,4-tetrahydrobenzo[h]quinazoline 4. Subsequently, this intermediate was acylated with 2-chloroacetyl chloride in the presence of triethylamine and under an inert atmosphere, obtaining the compound 2-chloro-1-(3-(naphthalen-1-yl)-3,4-dihydrobenzo[h]quinazolin-1(2H)-yl)ethan-1-one 5. In the third step, an intramolecular Friedel–Crafts cyclization was carried out using aluminum trichloride as a catalyst, yielding 2-(naphthalen-1-yl)-1,2,3,6-tetrahydro-5H-isoquinolino[8,1,2-hij]quinazolin-5-one 6. Finally, the reduction of this lactam with phosphorus pentachloride and sodium borohydride under anhydrous conditions led to the further closure of the polycyclic system, yielding the final product 1. The proposed route demonstrates the feasibility of using TATD 2 as a versatile precursor for constructing condensed heterocyclic systems of structural interest and potential relevance in advanced organic synthesis.

Organics doi: 10.3390/org7010011

Authors: Alexander V. Aksenov Nicolai A. Aksenov Nikolai A. Arutiunov Dmitrii A. Aksenov Anna M. Zatsepilina Daria I. Murashkina Maksim O. Shcheglov Sergei N. Ovcharov

2-Aryl-2-(3-indolyl)acetohydroxamic acids have emerged as promising antitumor agents; however, their poor pharmacokinetic profile remains a significant drawback. To address this limitation, we have synthesized a homolog of such acids—specifically 2-aryl-2-(3-indolyl)propionic acid (IC50 > 100 mM (U87)), along with several other derivatives: ethyl ester (IC50 > 100 mM (U87)), hydroxamate (IC50 21.2 ± 1.0 mM (U87)) and hydrazide (IC50 > 100 mM (U87)). The cytotoxicity of these compounds against glioblastoma cell lines was evaluated and compared to that of the parent acetohydroxamic acid derivatives.

Organics doi: 10.3390/org7010010

Authors: Yoonha Hwang Yeo Jin An Soohyun Sim Minjeong Shin

Understanding Li+ solvation structure is critical for the rational design of high- and localized high-concentration electrolytes. Here, we present a systematic investigation of tetrahydrofuran (THF)-based electrolytes with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) using Raman spectroscopy and 7Li nuclear magnetic resonance to investigate the local solvation structures. By varying the THF:LiTFSI molar ratio, we observed a transition of Li+ solvation from solvent-separated ion pairs to contact ion pairs and aggregates, accompanied by increased structural heterogeneity and constrained local dynamics. Raman spectroscopy captures the evolution of Li+–anion coordination with increasing salt concentration, while 7Li NMR chemical shifts, line widths, and relaxation times provide complementary insight into changes in the electronic environment and symmetry of Li+ coordination. Electrolyte structure is further examined by introducing a hydrofluoroether co-solvent into a concentrated (THF)2–LiTFSI electrolyte. Raman results show that the local Li+–TFSI− coordination structure is preserved upon 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) addition, whereas NMR reveals subtle modifications of the ion-rich solvation clusters. These results provide fundamental insight into Li+ solvation and electrolyte localization, offering general design principles for advanced electrolyte systems.

Organics doi: 10.3390/org7010009

Authors: Hirokazu Okamoto Ayane Nomoto Dahiru Umar Liman Akib Bin Rahman Toshifumi Tojo Shin Aoki

Protein phosphorylation and dephosphorylation reactions of intracellular molecules catalyzed by enzymes such as kinases and phosphatases are essential reactions in a lot of cellular functions such as intracellular signal transduction in living systems. The design and synthesis of artificial enzyme mimics are important research topics in bioorganic and bioinorganic chemistry. In this paper, we report on the construction of artificial phosphatases via the supramolecular self-assembly of compounds such as an amphiphilic bis(Zn2+-cyclen) (cyclen = 1,4,7,10-tetraazacyclododecane) complex, barbital derivatives modified with benzocrown ethers and boronophenyl groups, and a copper(II) ion in a two-phase solvent system. We have developed a hypothesis whereby a mono(4-nitrophenyl)phosphate (MNP) substrate coordinates to the Cu2(µ-OH)2 core in supramolecular complexes and is activated either by Lewis acidic units such as alkali metal (Li+, Na+ and K+)-benzocrown ether complexes or by boronophenyl moieties. The findings suggest that supramolecular phosphatase functionalized with a benzo-12-crown-4-Li+ complex shows a higher level of activity in the MNP hydrolysis of a two-phase solvent system compared with that of our previous supramolecular phosphatases in terms of hydrolysis activity and catalytic turnover.

Organics doi: 10.3390/org7010008

Authors: Krzysztof K. Zborowski Urszula Lelek-Borkowska

This study aims to investigate the relative stability of the diaminodinitroethylene isomers (cis, trans, and gem). To achieve this goal, calculations at several levels of theory were carried out. The B3LYP, PBE0, and CAM-B3LYP functionals, based on density functional theory (DFT), were used. G4 and MP2 calculations were also executed. All calculation methods predicted that the gem isomer is the most stable, while the cis isomer is the least stable. The energy order obtained for the isomers studied was rationalized by analysis of the detected intramolecular hydrogen bonding, electron delocalization, charge distribution, and changes in atomic energies in the structures studied. The origins of the superior stability of the gem isomer are demonstrated and justified.

Organics doi: 10.3390/org7010007

Authors: Maria E. Filkina Lev A. Lintsov Victor A. Tafeenko Maxim E. Kukushkin Elena K. Beloglazkina

1,3-Dipolar cycloaddition reactions of nitrile imines are a powerful tool for the construction of spirocyclic frameworks, yet controlling chemoselectivity remains challenging when dipolarophiles contain multiple reactive sites. In this study, we investigated the cycloaddition of nitrile imines with 5-arylmethylene-2-methylthiohydantoins, which possess both exocyclic C=C and endocyclic C=N bonds. Nitrile imines were generated from hydrazonoyl chlorides under basic conditions and reacted with the thiohydantoin substrates under optimized reaction conditions. The cycloaddition proceeded smoothly, affording spiro-fused thiohydantoin–pyrazoline derivatives. In all cases, the reaction occurred selectively at the exocyclic C=C bond, while the C=N bond remained unreactive even in the presence of excess dipole. This chemoselectivity is attributed to the greater steric accessibility of the exocyclic double bond. These results clarify key factors governing nitrile imine chemoselectivity and provide a reliable approach to structurally complex spirocyclic thiohydantoin derivatives.

Organics doi: 10.3390/org7010006

Authors: Felipe Pinto Isadora Barbosa Frederico Conceição F. A. Olguin Gabrielle Peiter Julia C. M. Willig Helio A. Stefani Giancarlo V. Botteselle Flavia Manarin

A sustainable hybrid material, CuO/Cu2O, was synthesized using an aqueous extract of Curcuma longa L. as a reducing and stabilizing agent. The material was characterized by UV-Vis spectroscopy, FTIR, XRD, SEM, EDX, and TEM. XRD analysis revealed peaks corresponding to CuO and Cu2O phases with crystallite sizes of 15.88 nm and 16.71 nm, respectively. TEM images showed nearly spherical particles with some agglomeration and an average particle diameter of 8.17 nm. The hybrid material exhibited catalytic activity toward the synthesis of 1,2,3-triazoles in water, under low catalyst loading and mild reaction conditions. This work highlights the potential of Curcuma longa-mediated synthesis as a low-cost, eco-friendly alternative for producing efficient catalysts, contributing to the advancement of green chemistry and sustainable nanomaterial applications in organic synthesis.

Organics doi: 10.3390/org7010005

Authors: Wenqiao Zhou Chunming Liu

Commercially available resorufin was shown to function as an organic photocatalyst for visible-light-induced aqueous radical polymerization under low-irradiance illumination. Polymers with narrow molecular weight distributions and high monomer conversions were successfully synthesized from acrylate and acrylamide monomers. The photopolymerization catalyzed by resorufin was consistent with a reductive quenching mechanism. Good temporal control of the reaction was achieved by toggling visible light irradiation.

Organics doi: 10.3390/org7010004

Authors: Lin Lei Linjian Wu Yongjian Qiu Yaju Chen

The development of a metalloenzyme-like catalytic system for the efficient oxidation of olefins under a dioxygen (O2) atmosphere at room temperature is of significant interest in the field of catalysis. Herein, we present a highly active and selective aerobic epoxidation of olefins using metalloenzyme-like catalysts based on a non-heme ligand, tris(2-pyridylmethyl)amine (TPA). Notably, manganese chloride complexed with TPA (Mn(TPA)Cl2) demonstrated excellent activity for the epoxidation of trans-stilbene using O2 as the oxidant in the presence of a co-reductant at 30 °C. A quantitative conversion of 99% and high yield of 98%, as determined by gas chromatography using an external standard method, were achieved under optimum reaction conditions. Furthermore, Mn(TPA)Cl2 exhibited a good substrate tolerance to styrene derivatives with electron-withdrawing or electron-donating groups, cyclic olefins with different substituents and substitution degrees, as well as long-chain olefins. Coupled with a high turnover frequency (TOF) of up to 30,720 h−1, these results underscore the potential of Mn(TPA)Cl2 as a promising metalloenzyme-like catalytic platform for the aerobic synthesis of diverse epoxides from olefins under ambient conditions.

Organics doi: 10.3390/org7010003

Authors: Chinyere Chidimma Enyi Gloria Ihuoma Ndukwe Godswill Kuta Fekarurhobo Michael Oelgemöller

In this study, the singlet oxygen photosensitization potential of three natural African plant extracts was investigated using the photooxygenation of α-terpinene (1). Utilizing visible light, the Carpolobia lutea extract achieved high conversions towards the anthelmintic ascaridole (2) of >60% after 90 min of irradiation, while the extracts of Hibiscus sabdariffa and Justicia secunda failed to induce significant photoreactivity. Quenching using 1,4-diazabicyclo[2.2.2]octane (DABCO) confirmed a singlet oxygen pathway for irradiation with the C. lutea extract. Further separation of the C. lutea extract and subsequent photooxygenation screening established several active fractions for ascaridole generation. Advanced HPLC–MS analyses of these active fractions revealed several photosensitizing constituents. These findings establish C. lutea extract as a sustainable and effective photosensitiser with comparable performance to commercial dyes.

Organics doi: 10.3390/org7010002

Authors: Wei Wu Takahiro Kojima Hiroshi Sakaguchi

A conjugated helical cage, comprising two 1,3,5-tris(phenylethynyl)benzene units connected by diyne linkers, was successfully synthesized. X-ray crystallography revealed helical molecular structures with large twisted angles and a 1:1 mixture of P- and M-enantiomers. Variable-temperature-NMR measurement indicated the racemization process between the enantiomers occurs rapidly on the NMR timescale. The rapid interconversion is attributed to the flexible diyne linkages, even though they were believed to be rigid.

Organics doi: 10.3390/org7010001

Authors: Sung-Jen Hung Lo-Yun Chiang Yi-An Hong Kai-Chih Chang Yang-Je Cheng Hsin-Ying Wu Hussana Hamid Anren Hu Tzenge-Lien Shih Hao-Ping Chen

Our previous study demonstrated that thiophene-substituted synthetic curcumin analogs possessed better antibacterial activity and stability than natural curcumin, demethoxycurcumin, or bisdemethoxycurcumin in antibacterial photodynamic therapy (aPDT). In addition, the activity of the furan-substituted analogs was weaker than that of the thiophene-substituted compounds. As oxygen, sulfur, and selenium belong to the same group in the periodic table, the antibacterial and anticancer activities of these three different elemental analogs were compared and investigated. The thiophene-substituted analog (compound 3) exhibited the most potent antibacterial activity in aPDT experiments. However, the furan-substituted analog (compound 1) exhibited the most potent anticancer activity. These results indicate that the differences in atomic radii or energy levels in these compounds produce different cell-attack results on generated free radicals. Ruthenium(II) complexes have a good reputation for use in PDT for cancer treatment. Our results show that complexation of ruthenium(II) with thiophene-substituted curcumin analogs does not enhance their antibacterial or anticancer activity.

Organics doi: 10.3390/org6040054

Authors: Jovana S. Dragojević Žiko Milanović Kristina Milisavljević Nevena Petrović Jelena Petronijević Nenad Joksimović Vera M. Divac Marijana Kosanić Marina D. Kostić

A novel series of Schiff bases (3a–3k), incorporating tranexamic acid (TXA) and phenol-derived aldehydes via imine linkers, was synthesized and structurally characterized. The antimicrobial activity of the compounds was evaluated against a range of clinically and environmentally relevant bacterial and fungal strains. Among them, derivatives 3i and 3k, bearing bromine and chlorine substituents on the phenol ring, exhibited the most potent antimicrobial effects, particularly against Penicillium italicum and Proteus mirabilis (MIC as low as 0.014 mg/mL). To elucidate the underlying mechanism of action, in silico molecular docking studies were conducted, revealing strong binding affinities of 3i and 3k toward fungal sterol 14α-demethylase (CYP51B), with predicted binding energies surpassing those of the reference antifungal ketoconazole. Additionally, UV-Vis and fluorescence spectroscopy assays demonstrated good stability of compound 3k in PBS and its effective binding to human serum albumin (HSA), respectively. ADMET and ProTox-II predictions further supported the drug-likeness, low toxicity (Class 4), and favorable pharmacokinetic profile of compound 3k. Collectively, these findings highlight TXA–phenol imine derivatives as promising scaffolds for the development of next-generation antimicrobial agents, particularly targeting resistant fungal pathogens.

Organics doi: 10.3390/org6040053

Authors: Giovanni Bella Giuseppe Bruno Antonio Santoro

Density functional theory (DFT) and its extension, time-dependent DFT (TD-DFT), have become fundamental tools for modeling chiral excited states and supporting experimental chiroptical spectroscopies. In this connection, the interest in understanding the asymmetric emission through the circularly polarized luminescence (CPL) technique peaked in the current decade. In the present work, we are computationally faced with an emerging class of luminophores which combines the luminogenic source of the BODIPY unit with the intrinsic chirality of the helicene pendant to obtain a chiral radiative deactivation. In particular, a meso-substituted BODIPY-[6]helicene was deeply examined through a DFT multistep approach to attain an appreciable level of theory for the CPL simulation. Among the multitude of alternatives, TPSSTPSS exchange-correlation functional with 6-311G(d,p) basis set revealed to be the best computational protocol to emulate the CPL spectral profile with regard to peak intensity, band position, and chiral sign for both M and P form.

Organics doi: 10.3390/org6040052

Authors: Mina Dumre Pandey Tahir Awais Krishna Pandey Samsul Arafin Eli Jones Kyle N. Plunkett

The direct chlorination, bromination and azidation of beta keto esters, 2-acetyl-1-tetralone and methyl 1-oxo-2,3-dihydro-1H-indene-2-carboxylate is achieved utilizing anion-coordinated hypervalent iodine benziodazoles derived from hypervalent iodine macrocycles. This reaction, which introduces the halogen, azido or cyano group at the alpha carbon atom of beta keto esters, is accomplished in chloroform at 60 °C and results in the formation of a chiral center. Depending on the structure of the benziodazole reagent, the reaction can have mild enantioselectivity. The reaction between 2-acetyl-1-tetralone and phenylalanine-derived hypervalent iodine benziodazoles results in the chlorinated product with 26% enantiomeric excess.

Organics doi: 10.3390/org6040051

Authors: Polidoros Chrisovalantis. Ioannou Nikolaos Tsoureas Sevasti-Panagiota Kotsaki

The synthesis of a small library of fused Cyclic Aryl Amino Carbon (f-CArAC) carbene precursors in the form of 1,1,2,4-tetraaryl-1H-isoindol-2-ium triflate (6), (7-R) (R = tBu, CF3) or 3,3-dimethyl-2,8-bis-arene-substituted-3,4-dihydro-isoquinolin-2-ium hydrogen-dichloride (8) and 2,4,8-tri(substituted)-isoquinolin-2-ium tosylate salts (12) has been achieved. All of them feature an arene incorporated on the annulated benzene ring of the corresponding heterocycle, introduced at the early stages of their synthesis via the Suzuki cross-coupling reaction between 2,6-dibromo-benzaldehyde and the desired aryl boronic acid. The terphenyl-2′carbaldehyde by-products of this Suzuki reaction are useful starting points for the preparation of two new iminium iodide salts (10-R) (R = H, CF3) as potential precursors to access ACyclic Amino Carbon (ACAC) carbenes. Compounds (6) and (7-tBu) react readily with hydroxide either in THF or in a biphasic Et2O/aqueous OH− solution to produce the substituted isoindolinols (13) and (14), respectively. The thermal dehydration of the former generates the corresponding f-CArAC carbene in situ, which is trapped by Cu(I)Cl furnishing, a rare example of a two-coordinate Cu(I) complex (15) supported by this new ligand scaffold.

Organics doi: 10.3390/org6040050

Authors: Gaëtan Ossard Milene Macedo Hornink Sabrina Lebrequier David-Alexandre Buisson Jean-Christophe Cintrat Eugénie Romero

High-Throughput Experimentation has undergone an outstanding evolution in the past two decades and has proven to be a game-changer in the acceleration of reaction discovery and optimization. Despite a good implementation in the pharmaceutical industry and a demonstrated accessibility to the technology, the generalization of High-Throughput Experimentation as a standard method for optimizing reactions is not yet observed. The perspective aims at discussing the necessity of generalizing such technologies, supported by the case study: the optimization by High-Throughput Experimentation of a key step in the synthesis of Flortaucipir, an FDA-approved imaging agent for Alzheimer’s diagnosis.

Organics doi: 10.3390/org6040049

Authors: Shaima Hkiri Neslihan Şahin Romain Sabourin Rémi Brandt İsmail Özdemir David Sémeril

A series of five cobalt(II) complexes, dichloro-bis(1-benzyl-benzimidazole)-cobalt(II) (1a), dichloro-bis[1-(4-fluorobenzyl)-benzimidazole]-cobalt(II) (1b), dichloro-bis((Z)-1-styryl-benzimidazole)-cobalt(II) (1c), dichloro-bis[(Z)-1-(2-fluorostyryl)-benzimidazole]-cobalt(II) (1d) and dichloro-bis(1-cinnamyl-benzimidazole)-cobalt(II) (1e), were evaluated in ethylene dimerization. Four of these complexes were described for the first time and fully characterized by IR, elemental analysis, mass and NMR spectroscopy. In the solid state, the cobalt atom exhibited a typical tetrahedral geometry and was found to be coordinated to two chlorine atoms and two benzimidazole rings. In the presence of 20 bar of ethylene and diethylaluminium chloride as a co-catalyst, the complex with styryl substituents on the benzimidazole rings, complex 1c, exhibited the highest activity with a turnover frequency of 3430 mol(ethylene)·mol(Co)−1·h−1.

Organics doi: 10.3390/org6040048

Authors: Liling Pan Ke Yang

4H-Benzo[d][1,3]oxathiin-4-ones and 4H-benzo[d][1,3]dioxin-4-ones, as important classes of sulfur- or oxygen-containing heterocyclic compounds, possess significant application potential in the fields of pharmaceutical chemistry, agriculture, and the food industry due to their distinctive structural characteristics and diverse biological activities. In recent years, efficient synthetic strategies for these compounds have witnessed remarkable progress. This review summarizes significant advancements in the construction of these heterocycles from 2012 to the present.

Organics doi: 10.3390/org6040047

Authors: Cilong Chen Jinrui Liu Bangsen Li Dashuai Zhang Peisong Zhang Jianjun Shi Zaifeng Shi

Rubber material with high elasticity and viscoelasticity has become the most widely used universal material, and the study of the aging failure mechanism of rubber has been meaningful research in the polymer materials field. Cis-polyisoprene was employed to analyze the mechanism of oxidative degradation under artificial UV irradiation, and the GQDs/g-C3N4 photocatalysis with a 2D layered structure prepared by the method of microwave-assisted polymerization enabled to accelerate the degradation procedure. The results showed that the oxidation of cis-polyisoprene occurred during the irradiation for 3 days and the structure of cis-polyisoprene changed. The α-H of the double bond was attacked by oxygen to form hydroperoxide. Then, aldehydes and ketones generated as the addition reaction of double bonds occurred. The content of the hydrogen of C=C reduced, and the oxidative degradation was dominant at the initial aging stage. The crosslinking reaction was dominant at the final aging stage and the average molecular weight decreased from 15.49 × 104 to 8.78 × 104. The GQDs could promote the charge transfer and the photodegradation efficiency and inhibit the electron–hole recombination. The light capture ability of GQDs was improved after compositing with g-C3N4. The free radicals ·O22− generated after adding GQDs/g-C3N4 nanoparticles, and the molecular weight of cis-polyisoprene decreased to 5.79 × 104, with the photocatalytic efficiency increasing by 20%. This work provided academic bases and reference values for the application of photocatalysts in the field of natural rubber degradation and rubber wastewater treatment.

Organics doi: 10.3390/org6040046

Authors: Aigul E. Malmakova Alan M. Jones

This review offers a focused overview of the strategies used to build and modify phenothiazine (PTZ) derivatives. It covers both classical synthetic approaches and advances reported since 2014, including transition metal-catalyzed transformations and greener techniques, such as electrosynthesis, microwave-assisted reactions, and ultrasound-promoted methods. Each strategy is evaluated with respect to efficiency, scalability, and sustainability. In parallel, the review surveys the diverse bioactivity profiles of PTZ derivatives, ranging from antipsychotic, anticancer, and antimicrobial activities to emerging applications in photodynamic therapy and neuroprotection. By correlating synthetic accessibility with biological potential, this review provides an integrated perspective that highlights advances achieved since 2014 and outlines future opportunities for rational PTZ design and applications.

Organics doi: 10.3390/org6040045

Authors: Savina Stoyanova Milen G. Bogdanov

This study examined twenty-eight N-methylimidazolium ionic liquids (ILs) with various substituents and anions to assess their impact on the activity of Carnitine Acetyltransferase (CAT), an indispensable enzyme in human metabolism. In vitro experiments demonstrated that these compounds inhibited CAT in a concentration-dependent manner, with IC50 values ranging from 0.93 to 30.8 mM. Structural analysis of the ILs revealed the following structure–activity relationships: (i) the length of the hydrocarbon chain at N3 markedly affects CAT activity, with longer chains resulting in stronger inhibition; (ii) the degree of unsaturation and the presence of polar groups are not essential for increased activity; (iii) the effect of the anion aligns with the Hofmeister series. One of the most potent compounds, 1-decyl-3-methylimidazolium bromide [C10C1im]Br, was identified as a mixed inhibitor of CAT with a Ki of 0.77 mM. These findings raise concerns about the biocompatibility of commonly used imidazolium ILs, as they may interfere with fatty acid oxidation by inhibiting their cellular transport.

Organics doi: 10.3390/org6040044

Authors: Diego Quiroga Jaime Ríos-Motta Augusto Rivera

4,4′-substituted-2,2′-((hexahydro-1H-benzo[d]imidazole-1,3(2H)-diyl)bis(methylene))bisphenols (1a–d) and 2,6-bis{[3-(2-hydroxy-5-substitutedbenzyl)octahydro-1H-benzimidazol-1-yl]methyl}-4-substitutedphenols (2a–b) were synthesized via microwave (MW) irradiation of aminal (2R,7R,11S,16S)-1,8,10,17-tetraazapentacyclo[8.8.1.1.8,170.2,70.11,16]icosane 2 with p-substituted phenols. Microwave (MW) irradiation improved reaction rates and yields at 80 °C. Compounds 1a–d were racemic, and 2a–b were diastereomeric. NMR spectra revealed key signals for the perhydrobenzimidazole fragment, aromatic rings, and aminal carbons. Differences in the 13C NMR spectra highlighted structural variations, such as distinct carbonyl and methoxyl signals in 2d. MW irradiation at higher temperatures (100–120 °C) reduced yields of 1, especially for phenols with methyl (Me) and methoxy (OMe) groups, suggesting a shift toward the formation of compound 2. Additionally, higher temperatures led to polymerization byproducts, emphasizing the impact of MW energy on reaction pathways. These results provide valuable insights for designing molecules with potential applications in materials science and medicinal chemistry.

Organics doi: 10.3390/org6030043

Authors: Péter Kisfaludi Sára Spátay Péter Huszthy Ádám Golcs

Although sulfonated acridines and acridones are valuable scaffolds in diagnostics and materials science, to our best knowledge, there is no comprehensive study that addresses how the degree of sulfonation depends on reaction parameters. To fill this gap, we investigated the sulfonation behavior of unsubstituted acridine and acridone under classical conditions, using sulfuric acid, oleum, and chlorosulfonic acid. A factorial experimental design was applied to systematically evaluate the influence of temperature and reagent excess on the extent of sulfonation, while keeping the reaction time constant. Products were analyzed by HPLC–MS/MS to determine the degree of sulfonation and its distribution. Regioselectivity and product isolation were not addressed in this study. Our results provide a foundational dataset for controlling sulfonation level for these heterocycles and can help future synthetic applications where defined sulfonation patterns are desired.

Organics doi: 10.3390/org6030042

Authors: Elisa Leyva Johana Aguilar Silvia E. Loredo-Carrillo Ismael Acosta-Rodríguez

Several fluoro phenyl triazoles were synthesized using click chemistry between fluoro phenyl azides and phenyl acetylene. Under ultrasound irradiation, this synthetic procedure was performed with Cu (I) in the presence of 1,10-phenanthroline. It is fast with high yields of target compounds. In addition, fluoro phenyl triazoles were evaluated against Candida albicans. The inhibition percentage of yeast growth was investigated using different concentrations of triazoles. Compounds containing a fluorine atom in 2, 4, 2,6, and 2,4,6 positions inhibited a higher percentage of yeast growth. All of the triazoles showed inhibition of the yeast–mycelium transition, which was related to pathogenicity of yeast strain C. albicans.

Organics doi: 10.3390/org6030041

Authors: Abdukhakim A. Ziyaev Sobirdjan A. Sasmakov Turdibek T. Toshmurodov Jaloliddin M. Abdurakhmanov Saidazim A. Ikramov Shukhrat Sh. Khasanov Oybek N. Ashirov Mavluda A. Ziyaeva Dilrabo B. Begimqulova

Derivatives of 1,2,4-triazole-3-thione exhibit a variety of biological activities, including antimicrobial (e.g., compounds 31d–k, 32d, 36f), antitumor (e.g., 71, 77a–c, 82g, 94h), anti-inflammatory, analgesic (100a, 102, 105), antidiabetic, and antioxidant (104, 138) activity. These compounds can be efficiently synthesized by classical methods (e.g., cyclization of thiosemicarbazides) and/or modern “green” approaches, which allow for obtaining target compounds in high yields (up to 96%). The presence of electron-donating groups (e.g., -OH, -OCH3) enhances antimicrobial and antitumor activity. Substituents in the aromatic ring (e.g., NO2, Cl) affect the ability to bind to biological targets such as DNA or enzymes. 1,2,4-triazole-3-thiones can also be used as fungicides and herbicides (e.g., 131), demonstrating high efficiency against phytopathogens. Thus, 1,2,4-triazole-3-thione derivatives are multifunctional compounds with high potential for the development of new drugs and agrochemicals. Their further study and modification can lead to the creation of more effective and safer drugs.

Organics doi: 10.3390/org6030040

Authors: Wender Alves Silva Sayuri Cristina Santos Takada Felipe Marques Nogueira Luiz Arthur Ramos Almeida

Catalytic transfer hydrogenation (CTH) and microwave-assisted organic synthesis (MAOS) have each advanced the sustainability of reduction chemistry; however, their combined application to conjugated enones remains largely unexplored. To the best of our knowledge, no unified protocol has been reported for the rapid, one-pot conversion of chalcones into saturated alcohols under microwave irradiation. Herein, we report a concise and green method that integrates MAOS with Pd/C-catalyzed CTH, employing inexpensive ammonium formate in ethanol. In contrast to state-of-the-art hydrogenations that require pressurized H2 or costly metal complexes, our strategy (i) achieves complete conversion within 20 min at 60 °C, (ii) tolerates both electron-rich and electron-poor substrates, (iii) reduces nitro-substituted chalcones in a single step, and (iv) consumes < 0.005 kWh per reaction—an approximately 250-fold energy saving relative to conventional procedures. These results position microwave-driven CTH as a scalable alternative for synthesizing pharmacologically relevant saturated alcohol scaffolds from readily available chalcones.

Organics doi: 10.3390/org6030039

Authors: Jeremy A. Rodríguez-Vargas Sebastián H. Díaz-Rodríguez Víctor G. Vergara-Rodríguez Ángel Vidal-Rosado Cristtian Rivera-Torres Alejandra Ríos-Rodríguez Martín Rodríguez-Del Valle Daliana Agosto-Disdier Marielys Torres-Díaz Kai H. Griebenow Raúl R. Rodríguez-Berríos

The search for bioactive compounds with antioxidant properties is critical in combating oxidative stress-related diseases and advancing novel therapeutic agents. Azo dyes, traditionally used in textiles, food, and cosmetics, have recently attracted attention due to their emerging biological activities, including antioxidant potential. In this study, we synthesized and characterized 267 azo dyes derived from natural phenolic cores such as salicylic acid, syringol, and 5,6,7,8-tetrahydro-2-naphthol. Eighteen of these compounds are novel. Structural characterization was performed using NMR, UV-Vis, IR spectroscopy, and mass spectrometry. Antioxidant activity was assessed using in vitro assays with ABTS radical scavenging method. SAR analysis revealed that dyes derived from syringol and 5, 6, 7, 8-tetrahydro-2-naphthol showed the most consistent and potent antioxidant activity. Notably, azo dyes bearing fluoro and nitro substituents in the para position exhibited the lowest IC50 values, highlighting the influence of electron-withdrawing groups and substitution patterns on antioxidant behavior. This work establishes a precedent for SAR-driven evaluation of azo dyes using ABTS and supports their further exploration as functional antioxidant agents in medicinal chemistry.

Organics doi: 10.3390/org6030038

Authors: María Isabel Amil-Miranda Armando Pineda-Contreras Francisco Javier Martínez-Martínez Marcos Flores-Álamo Hector García-Ortega Juan Saulo González-González

Phenytoin is an anticonvulsant drug that suffers from low aqueous solubility. The formation of phenytoin salts is a strategy employed to address this issue. A phenytoin–piperidine salt (PPD–PNT) was synthesized by solvent-assisted grinding and characterized by infrared (IR) spectroscopy, 1H and 13C Nuclear Magnetic Resonance (NMR), and powder and single crystal X-ray diffraction. The IR and NMR spectra obtained differed from those of the starting compounds, showing shifts in the N-H and C=O group signals, as well as the appearance of NH+ signals, indicating proton transfer and salt formation. Powder X-ray diffraction confirmed the formation of a new solid phase corresponding to the salt. Single crystal X-ray diffraction showed the molecular structure of the PPD–PNT salt.

Organics doi: 10.3390/org6030037

Authors: Luis A. Méndez-Delgado Mónica Martínez-Montiel Alma Fuentes-Aguilar Socorro Meza-Reyes Sara Montiel-Smith José Luis Vega-Baez José M. Padrón Penélope Merino-Montiel

A total of 24 novel steroidal derivatives were synthesized, including 1,3,4-thia(selena)diazolines and structurally unique spirothiadiazolines, obtained through intramolecular cyclization under standard acetylation conditions. This strategy was further extended to the construction of a novel dimeric compound bearing a thiadiazoline linker. Seleno- and thiosemicarbazone precursors were derived from various functionalized steroidal monomers and dimers via straightforward synthetic protocols. Key intermediates included aldehyde 7 and ketones 16, 19, and 24. Rotameric equilibria were observed in certain thiosemicarbazones, attributed to partial double-bond character in the N–CS bond. Cyclization yielded heterocyclic systems as epimeric mixtures, and in some cases, inseparable mixtures of isomers were obtained due to low diastereoselectivity. Full structural elucidation of epimeric pairs was achieved using 2D NMR and IR spectroscopy, with compounds 2, 3, 5, 11, 17, 27, 28a, and 28b further confirmed by single-crystal X-ray diffraction. Preliminary antiproliferative assays against human cancer cell lines revealed GI50 values below 10 µM for compounds 21, 22, and 27.

Organics doi: 10.3390/org6030036

Authors: Liping Wang Mingyu Zhang

Porous carbon-loaded MnO was prepared via a combination of the sol–gel method and the chemical blow molding method using polyvinylpyrrolidone (PVP) and manganese nitrate as starting materials. SEM, EDX, TEM, FTIR, XRD, XPS, nitrogen adsorption–desorption, and elemental analysis were used to assess its physical and chemical characteristics. Furthermore, the adsorption property of porous carbon-loaded MnO for hexavalent chromium (Cr(VI)) in polluted water was investigated in detail. The results demonstrated that large numbers of MnO nanoparticles were evenly mounted on the surfaces of carbon walls, with a uniform distribution of C, N, and O elements. The BET surface area was 46.728 m2/g, and the pore sizes of porous carbon ranged from 2 nm to 10 nm. Additionally, abundant surface functional groups were found in porous carbon-loaded MnO, a result consistent with XPS data and applicable to the adsorption of heavy metals from aqueous solutions containing Cr(VI). The Freundlich model fitted the adsorption isotherm well, and the pseudo−second−order model precisely matched the adsorption kinetics. According to the study results, the adsorption was multilayer, and the adsorption process involved an endothermic reaction. These results indicate that this is a feasible way to synthesize a high−efficiency adsorbent for the removal of harmful heavy−metal ions from wastewater.

Organics doi: 10.3390/org6030035

Authors: Suzana Apostolov Dragana Mekić Marija Mitrović Slobodan Petrović Gyöngyi Vastag

Modern agriculture relies heavily on the use of pesticides, with one-third of them being herbicides. Chloroacetamides are the most widely used herbicides because of their high effectiveness, but their extensive use poses environmental challenges and threatens the health of living organisms due to toxicity risks. Since the pharmacokinetic behavior and toxicity of a compound are influenced by its lipophilicity, this essential physicochemical parameter for disubstituted chloroacetamides was determined in silico and experimentally through thin-layer chromatography on reversed phases (RPTLC C18/UV254s) in mixtures of water and distinct organic modifiers. The pharmacokinetic profile of chloroacetamides was analyzed by using the BOILED-Egg model. The correlation between the obtained chromatographic parameters and software-based lipophilicity, pharmacokinetic, and ecotoxicity predictors of the studied chloroacetamides was assessed by using linear regression, but more comprehensive insight was obtained through multivariate methods—Cluster Analysis and Principal Component Analysis. It was observed that the total number of carbon atoms in the structure of their molecules, along with the type of hydrocarbon substituents, are the most important factors affecting lipophilicity, pharmacokinetics, and potential toxicity to non-target organisms.

Organics doi: 10.3390/org6030034

Authors: Lucia Emanuele Maurizio D’Auria

DFT calculations at the B3LYP/aug-cc-pVDZ level of theory on some aromatic substrates showed that in the HOMO (Highest Occupied Molecular Orbital) of nitrobenzene, the atomic coefficients are not in agreement with the meta-directing behavior of this compound. The atomic coefficients are the same in the ortho and in the meta positions. The HOMO (or NHOMO (Next Occupied Molecular Orbital) in the case of benzaldehyde) is not in agreement with the experimental results when deactivating, meta-orienting compounds are considered. Mulliken charges sometimes are not able to explain the observed reactivity. Hirshfeld charges allow us to predict the orientation of the attack of an electrophile on the aromatic ring, with the exception of nitrobenzene. Both HOMO atomic coefficients and charges are in agreement with the experimental results when deactivating, ortho-para orienting, and activating compounds are tested.

Organics doi: 10.3390/org6030033

Authors: Mengran Chen Dongmei Xie Hongqing Zhou Pengan Zong

Polyaniline (PANI) based thermoelectric materials have attracted much attention in flexible energy harvesting devices due to their unique molecular structure, excellent chemical stability, and low cost. However, the intrinsic thermoelectric performance of intrinsic PANI makes it difficult to meet the needs of practical applications due to its low electronic transport properties. This review focuses on the preparation methods and key strategies for developing high-performance PANI-based thermoelectric materials. It aims to comprehensively update knowledge regarding synthesis methods, microstructures, thermoelectric properties, and underlying mechanisms. The overall goal is to provide timely insights to promote the development of high-performance PANI-based thermoelectric materials.

Organics doi: 10.3390/org6030032

Authors: Lei Li

Ultra-high-molecular-weight polyethylene (UHMWPE) is a pivotal material in engineering and biomedical applications due to its exceptional mechanical strength, wear resistance, and impact performance. However, its extreme melt viscosity, caused by extensive chain entanglements, severely limits processability via conventional melt-processing techniques. Recent advances in catalytic synthesis have enabled the production of disentangled UHMWPE (dis-UHMWPE), which exhibits enhanced processability while retaining superior mechanical properties. Notably, heterogeneous catalytic systems, utilizing supported fluorinated bis (phenoxy-imine) titanium (FI) catalysts, polyhedral oligomeric silsesquioxanes (POSS)-modified Z-N catalysts, and other novel catalysts, have emerged as promising solutions, combining structural control with industrial feasibility. Moreover, optimizing polymerization conditions further enhances chain disentanglement while maintaining ultra-high molecular weights. These systems utilize nanoscale supports and ligand engineering to spatially isolate active sites, tailor the chain propagation/crystallization kinetics, and suppress interchain entanglement during polymerization. Furthermore, characterization techniques such as melt rheology and differential scanning calorimetry (DSC) provide critical insights into chain entanglement, revealing distinct reorganization kinetics and bimodal melting behavior in dis-UHMWPE. This development of hybrid catalytic systems opens up new avenues for solid-state processing and industrial-scale production. This review highlights recent advances concerning interaction between catalyst design, polymerization control, and material performance, ultimately unlocking the full potential of UHMWPE for next-generation applications.

Organics doi: 10.3390/org6030031

Authors: Juan F. Ortuño Alessio Ghisolfi Raquel Almansa Olga Soares do Rego Barros Ana Sirvent José M. Sansano Francisco Foubelo

The synthesis of cannabigerol—a cannabinoid with significant pharmaceutical potential—is described. The synthesis involves four stages. In the first step, (E)-non-3-en-2-one reacts with dimethyl malonate to yield a cyclic enone, which is subsequently oxidized with bromine to produce the olivetol ester. This ester then undergoes an alumina-catalyzed coupling reaction with geraniol, followed by ester hydrolysis to obtain cannabigerol. By modifying the chain length of the enone in the initial step and employing allylic alcohols other than geraniol, a range of cannabigerol derivatives can be synthesized, including the natural product cannabigerovarin.

Organics doi: 10.3390/org6030030

Authors: Jingwei Wu Yongzhu Zhou Lei Zhang Jie Zhang Pei Song Xiaoling Wang Cuihong Wang

Density functional theory calculations were performed to elucidate the mechanistic details and origins of the selectivity of the nickel-catalyzed hydroboration of vinylarenes using B2pin2/MeOH. The catalytic cycles involved four sequential elementary steps: hydronickelation, anion exchange, transmetalation, and reductive elimination. Kinetic analyses identified hydronickelation as the rate-determining step with an activation barrier of 19.8 kcal/mol, while transmetalation proceeded through a stepwise mechanism characterized by two distinct transition states. Comprehensive analyses of the relevant transition structures and energetics demonstrated that the observed R-enantioselectivity (94% ee) originated from favorable nonbonding interactions. Lastly, our calculations suggested that the Markovnikov regioselectivity was predominantly governed by steric factors rather than electronic effects.

Organics doi: 10.3390/org6030029

Authors: Raúl R. Rodríguez-Berríos José A. Prieto

Hydroxymethyl 1,3-diol motifs are common structural motifs in natural products, particularly in polypropionates with important therapeutic potential. However, general and complementary methods for their regio- and diastereoselective synthesis remain limited. In this study, we expanded a second-generation epoxide-based methodology involving the regioselective cleavage of TIPS-monoprotected cis- and trans-2,3-epoxy alcohols using alkenyl Grignard reagents. Regioselective ring opening of cis-epoxides provided anti-1,3-diols, while trans-epoxides afforded the corresponding syn-1,3-diols. The use of cis-propenylmagnesium bromide and vinyl Grignard reagents enabled direct access to cis- and terminal homoallylic 1,3-diols, respectively, with moderate to good yields (46–88%) and excellent regioselectivities (95:5). In contrast, reactions with trans-propenyl Grignard reagent led to partial alkene isomerization, limiting their synthetic utility. To address this, a complementary two-step approach employing propynyl alanate addition followed by sodium/ammonia reduction was incorporated, providing access to trans-homoallylic 1,3-diols with high diastereoselectivity. All 1,3-diols were characterized by NMR spectroscopy, confirming regioselective epoxide opening. These combined strategies offer a practical and modular platform for the synthesis of syn- and anti-hydroxymethylated 1,3-diols and their application to the construction of polypropionate-type fragments, supporting future efforts in the total synthesis of polyketide natural products.

Organics doi: 10.3390/org6030028

Authors: Ricardo Cartes-Velásquez Felipe Morales-León Franco Valdebenito-Maturana Pablo Sáez-Riquelme Nicolás Rodríguez-Ortíz Hernán Carrillo-Bestagno

Vancomycin, a cornerstone antibiotic against severe Gram-positive infections, is increasingly challenged by resistance in Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin Enterococcus spp. (VRE), necessitating the development of novel therapeutic strategies. This review examines how structural modifications to vancomycin can enhance its antibacterial activity and explores the critical role of computational approaches in designing the next generation of analogs. By analyzing the existing literature, we highlight how strategic alterations, such as the introduction of lipophilic side chains, substitutions on the sugar moieties, and modifications to the aglycone core, have yielded derivatives with improved antibacterial potency. Notably, certain analogs (e.g., Vanc-83, Dipi-Van-Zn) have demonstrated expanded activity against Gram-negative bacteria and exhibited enhanced pharmacokinetic profiles, including prolonged half-lives and improved tissue penetration, crucial for effective treatment. Semisynthetic glycopeptides like telavancin, dalbavancin, and oritavancin exemplify successful translation of structural modifications, offering sustained plasma concentrations and simplified dosing regimens that improve patient compliance. Complementing these experimental efforts, computational methods, including molecular docking and molecular dynamics simulations, provide valuable insights into drug–target interactions, guiding the rational design of more effective analogs. Furthermore, physiologically based pharmacokinetic modeling aids in predicting the in vivo behavior and optimizing the pharmacokinetic properties of these novel compounds. This review highlights a critical path forward in the fight against multidrug-resistant infections. By meticulously examining the previously carried out structural refinement of vancomycin, guided by computational predictions and validated through rigorous experimental testing, we underscore its immense potential.

Organics doi: 10.3390/org6020027

Authors: Danielle Tapia Bueno Amanda Fonseca Leitzke Rayane Braga Martins Daisa Hakbart Bonemann Emanuel Gomes Bertizzolo Gabrielly Quartieri Sejanes Juliana Porciúncula da Silva Lucas Minghini Gonçalves Neftali Lenin Villarreal Carreno Claudio Martin Pereira de Pereira

Papilloscopy, the science of human identification through fingerprints, has seen notable advancements in developing less toxic latent fingerprint developers (LFDs), especially from natural feedstock. Tannins, the second most abundant natural polyphenol, present a potential eco-friendly and cost-effective alternative, with no record of their use as LFDs in the existing literature. This study characterized four types of tannins from black wattle, using Fourier Transform Infrared Spectroscopy, revealing key functional groups like C=O, C=C, and O–H. Ultraviolet–visible absorption spectra showed similar behaviors for all tannins, indicating phenolic and benzenoid structures. Energy-dispersive X-ray Spectroscopy identified high concentrations of chlorine, sodium, potassium, and sulfur, naturally found in biomass and soil. Finally, elements in significant concentrations, such as sodium, potassium, iron, zinc, and copper, were found through the incineration of the spent bark. On the basis of these findings, the tannin with the highest potential for LFD was selected. Combining this tannin with spent bark ash resulted in a composite whose performance was evaluated using different methods, including depletion studies, tests with various donors, and assessments on different surfaces. The results demonstrated that this combination significantly enhanced the material’s efficiency by integrating organic and inorganic properties, which improved visual contrast and powder adhesion.

Organics doi: 10.3390/org6020026

Authors: Zhikang Wang Mingjie Yang Weibo Yang Zhongzheng Gao Hui Zhao Gang Wei Jifu Sun

The interaction between cucurbit[8]uril (Q[8]) and the guest 1-methyl-4-(4-(1-methylpyridin-1-ium-4-yl)benzamido)pyridin-1-ium (PB2+) has been thoroughly investigated. Multiple techniques were employed, including 1H NMR spectroscopy, mass spectrometry, isothermal titration calorimetry (ITC), UV–vis absorption spectrophotometry, and quantum chemistry calculations. The experimental results and calculation analysis have clearly shown that in aqueous solution, the host Q[8] preferentially encapsulates the phenylpyridinium salt moiety of the PB2+ guest within its hydrophobic cavity, forming a 1:2 inclusion complex.

Organics doi: 10.3390/org6020025

Authors: Ying An Ying Sun Zhenming Yin

A macrocyclic receptor based on azopyrrole and polyether was synthesized, and its structure was characterized by NMR (1H and 13C), HRMS and X-ray crystallography. In the solid state, the macrocyclic molecules could bind methanol through a pair of N-H…O hydrogen bonds and further self-assembled into tubular structures through C-H…N hydrogen bonds. This revealed that the crystal could still keep its porous properties after the included molecules were removed. The UV–Vis titration indicates that the macrocylic receptor can chromogenically and selectively sense fluoride ion in DMSO solution, and the sensing mechanism was rationalized by 1H NMR.

Organics doi: 10.3390/org6020024

Authors: Artem P. Ermolenko Diana Y. Pobedinskaya Elena K. Avakyan Anastasia A. Borovleva Alexander N. Larin Ivan V. Borovlev Oleg P. Demidov

A series of previously poorly studied heterocyclic compounds, 10R-pyrido[4,3-a]phenazines, including the previously unknown parent compound, has been synthesized. The proposed synthetic approach is remarkable for its simplicity, due to the ease of the synthesis of the starting materials from readily available precursors, and is characterized by high yields of the target products, achievable under both acidic and basic catalysis. The paper discusses the synthesis conditions, optimization procedures, and X-ray crystallographic data.

Organics doi: 10.3390/org6020023

Authors: Isis Apolo Silveira de Borba Jamile Buligon Peripolli Angélica Rocha Joaquim Fernando Fumagalli

Heterocycle cores are widely used in medicinal chemistry for developing bioactive compounds. In this scenario, using cheap and accessible starting material to build these heterocycles is desirable to obtain new drug candidates for cost-efficient processes. One easily accessible source of starting material are amino acids. Usually, these compounds are employed in peptide synthesis, but their use for building heterocycle frameworks presents another appealing opportunity. Therefore, this review highlights the application of histidine and tryptophan, two heteroaromatic amino acids, in fused heterocyclic scaffold synthesis and their use in bioactive compounds.

Organics doi: 10.3390/org6020022

Authors: Tian Zhao Shilin Peng Jiangrong Yu Jiayao Chen Fuli Luo Pengcheng Xiao Saiqun Nie Yi Chen

Metal–organic frameworks (MOFs), particularly zirconium-based frameworks (Zr-MOFs), have gained significant attention in recent years due to their unique structural and functional properties. This review focuses on eco-friendly synthetic methods for producing Zr-MOFs, addressing the environmental impacts and costs associated with conventional synthesis, which often relies on hazardous reagents and harsh conditions. We explore various green synthesis strategies, including the selection of raw materials (such as using zirconium acetate), organic ligands (recycling waste materials for ligand synthesis), and synthesis methods (solvothermal, microwave-assisted, ultrasound-assisted, electrochemical, and mechanochemical approaches). Additionally, the application of Zr-MOFs in photocatalysis and electrocatalysis is examined, highlighting their potential for environmental purification and energy conversion. Despite the progress made in laboratory settings, challenges remain in achieving cost-effectiveness, material stability, and scalability for industrial applications. Future research should concentrate on enhancing synthesis efficiency, optimizing catalytic properties, investigating structure–property relationships, and expanding applications to novel catalytic reactions, thus ensuring Zr-MOFs can contribute to sustainable development in chemical science and technology.

Organics doi: 10.3390/org6020021

Authors: Maria C. Vagi Andreas S. Petsas Dionysia Dimitropoulou Melpomeni Leventelli Anastasia D. Nikolaou

This study concerns the investigation of the sorption and desorption phenomena of the organic dye methylene blue (MB) on three different marine sediments and non-living biomass of the seagrass species Posidonia oceanica. All tested adsorbents were of natural origin and were collected from unpolluted coasts of the North Aegean Sea (Greece). The batch equilibrium technique was applied and MB concentrations were determined by spectrophotochemical analysis (λ = 665 nm). The experimental results showed that all four isotherm models, Freundlich, Langmuir, Henry, and Temkin, could describe the process. The normalized to organic matter content adsorption coefficients (KOM) ranged between 33.0765 and 34.5279 for the studied sediments. The maximum adsorption capacity (qmax) of sediments was in the range of 0.98 mg g−1 and 6.80 mg g−1, indicating a positive correlation with the adsorbents’ organic matter content, textural analysis of fine fraction (<63 μm), and specific surface area. The bioadsorption of MB on P. oceanica biomass resulted in 13.25 mg g−1 up to 17.86 mg g−1 adsorption efficiency. Desorption studies revealed that the studied dye in most cases was very strongly adsorbed on studied matrices with extremely low quantities of seawater extractable amounts (≤1.62%). According to the experimental findings, phycoremediation by using P. oceanica can be characterized as an efficient method for the bioremediation of dye-polluted wastewater.

Organics doi: 10.3390/org6020020

Authors: Teresa Celestino

In the chemical education field, the Johnstone’s triangle represents three learning levels (symbolic, macroscopic, and molecular) needed for students. Afterwards, Mahaffy suggested a tetrahedron model based on this triangle, where the top represents the human element. Subsequently, Sjöström proposed a subdivision of the top into three other levels: applied chemistry, socio-cultural context, and critical–philosophic approach. These six dimensions of chemical knowledge will be examined in relation to the discovery of aniline, its chemistry and applications. The historical and epistemic aspects of this topic, gradually broadening the focus to the social, political, and artistic backdrop, can provide a more effective approach to teaching the subject. The major impact of the synthetic dye industry makes this field of study particularly important for a Bildung-focused chemistry education.

Organics doi: 10.3390/org6020019

Authors: Carlo Santulli Serena Gabrielli Graziella Roselli

Most bioplastics are based on polysaccharides, which are either synthesized from a variously sourced monomer or extracted from some biomass waste. In many cases, some lignocellulosic fibers are then added to the obtained bioplastics to form biocomposites and extend their range of applications beyond packaging films and generically easily biodegradable materials. Plant-extracted tannins, which, as such, might also be building blocks for bioplastics, do nonetheless represent a useful complement in their production when added to polysaccharide-based plastics and biocomposites, since they offer other functions, such as bioadhesion, coloration, and biocidal effect. The variety of species used for tannin extraction and condensation is becoming very wide and is also connected with the local availability of amounts of bio-waste from other productions, such as from the food system. This work tries to summarize the evolution and recent developments in tannin extraction and their increasing centrality in the production of polysaccharide-based plastics, adhesives, and natural fiber composites.

Organics doi: 10.3390/org6020018

Authors: Bálint Jávor Antal Agárdi Péter Kisfaludi Barnabás Frigyes Márton Temesvári Panna Vezse Tünde Tóth Péter Huszthy Ádám Golcs

Bipyridine ethers are commonly occurring structural motifs in supramolecular chemistry. The herein reported efforts aim to extend the synthetic platform of bipyridino-precursors with new bifunctional intermediates and to improve some previously reported synthetic strategies for structural analogues, like bipyridine-diols as common macrocycle precursors. In addition, their optimized and highly efficient oxidation to the corresponding dialdehydes is reported to obtain further reactive intermediates with wide modifiability. Furthermore, methylations of pyridine-carbaldehydes were carried out alongside different synthetic strategies to introduce chirality centers. Synthetic difficulties and some unsuccessful approaches are also reported to help in focusing future efforts.

Organics doi: 10.3390/org6020017

Authors: Danijela S. Kretić Marija I. Maslarević Dušan Ž. Veljković

Understanding the factors that affect the detonation performance of high-energy molecules (HEMs) is crucial for the design of novel explosives and fuels with desirable characteristics. While molecular factors, such as the presence of specific functional groups that give organic molecules explosive properties, are key determinants of detonation characteristics, other factors like the geometry of molecules in crystal structures can also affect the high-energy properties of materials. Although it is known that slight deviations in the crystal structure geometry affect the sensitivity of nitroaromatic explosives, the influence of these variations on detonation performance remains unknown. In this study, we extracted different crystal structures of the same high-energy nitroaromatic molecules from the Cambridge Structural Database and calculated their detonation velocities and pressures using the Kamlet–Jacobs equations. Results indicated that different geometries of the same crystal structure can lead to non-negligible differences in detonation velocities and pressures. In the case of the 2,4,6-triamino-1,3,5-trinitrobenzene molecule, discrepancies in detonation pressures among different crystal structures were calculated to be 7.68%. Analysis of geometrical arrangements showed that these differences are mainly the consequence of diverse non-covalent bonding patterns that affect crystal densities.

Organics doi: 10.3390/org6020016

Authors: Ayoub El-mrabet Amal Haoudi Youssef Kandri-Rodi Ahmed Mazzah

Quinolones represent one of the largest classes of synthetic antibiotics used in both human and veterinary medicine. Since the discovery of nalidixic acid, a substantial body of research has been carried out on quinolones, resulting in the synthesis of several quinolone derivatives with exceptional pharmacology. In addition to their antibacterial action, quinolones have a broad spectrum of diverse biological activities. In this regard, the present review examines the literature of recent years describing synthesis protocols, reactivity and biological properties, with particular emphasis on the antibacterial, antimalarial, antitrypanosomal, antileishmanial, antiviral and anticancer activities of this famous class of molecules. Finally, this review highlights the potential of quinolones as preferred pharmacophores in medicinal chemistry. The aim is to highlight the innovative aspects of the rational design of new therapeutic agents with this structural motif, in the face of emerging antibiotic resistance and the urgent need for new active molecules.

Organics doi: 10.3390/org6020015

Authors: Marcello Casertano Brian G. Kelly Malachi W. Gillick-Healy Paolo Grieco Mauro F. A. Adamo

Indole heterocycles have an established reactivity, and these compounds are H-bond donors via a peculiar non-basic NH. However, the indole core has been scarcely employed in organocatalysis, with only a few examples relevant to electrophilic halogenation reported. To expand the range of potential transformations achievable via indole catalysis, we have designed a set of new organic species incorporating an indole core, alongside three privelaged chiral moieties found in many known organocatalysts, namely a quaternary ammonium salt, a diamine and an amino-urea. Herein, we report an optimised synthetic route for the preparation of these potential catalytic species in an enantiomerically pure form. The syntheses are conceived to be modular and therefore will allow each of the three single organic catalysts to be expanded into families without alteration of the synthetic layout, therefore leading to a fast optimisation of new asymmetric procedures.

Organics doi: 10.3390/org6020014

Authors: Alam Yair Hidalgo Quirino Torres-Sauret Carlos Ernesto Lobato-García Erika Madeleyne Ramos-Rivera Luis Fernando Roa de la Fuente Abraham Gómez-Rivera Miguel Ángel Vilchis-Reyes Erika Alarcón-Matus Oswaldo Hernández-Abreu Nancy Romero-Ceronio

This study describes the efficient synthesis of five dinitrochalcones (DNCHs) using an ultrasonic bath as an unconventional method to improve reaction yields and reduce reaction times. The Claisen–Schmidt condensation of nitroacetophenones and nitrobenzaldehydes was carried out in a cyclohexane–methanol solvent system under ultrasonic irradiation, achieving yields between 56% and 92%. The application of ultrasound not only accelerated the reaction but also improved the overall efficiency compared to conventional methods such as magnetic stirring. The synthesized compounds were characterized by NMR spectroscopy, which corroborated their structures. Therefore, it is confirmed that obtaining DNCHs with a nitro group in ortho by ultrasonic irradiation is an energetically efficient and environmentally friendly alternative.

Organics doi: 10.3390/org6020013

Authors: Zuleyma Martínez-Campos Luis Eduardo Hernandez-Dominguez Fatima Romero-Rivera Diana López-López María Vicky Corona-González Susana T. López-Cortina Francisco José Palacios-Can Rodrigo Said Razo-Hernández Mario Fernández-Zertuche

γ-amino butyric acid (GABA) is an inhibitory neurotransmitter whose deficiency has been associated with various neurological disorders. However, its low liposolubility limits its use as a supplement. Thus, multiple investigations have focused on searching for lipophilic GABA analogs that can modulate the activity of the GABAB receptor, which could be associated with the etiology of some central nervous system disorders. The GABA analogs available on the market are Vigabatrin, Gabapentin as well as Pregabalin and Baclofen. In this work, we report on the synthesis of GABA analogs, taking the scaffold of GABA, Pregabalin, and Baclofen as a starting point. The analogs include structural features that could favor the affinity of the molecules for the GABAB receptor, such as heterocyclic rings in the γ-position and alkyl or p-Cl-phenyl substituents (in analogy to Pregabalin and Baclofen, respectively). These analogs were synthesized by a sequence of reactions involving an N-alkylation, a 1,4-conjugated addition of dialkyl and diarylcuprates and a basic hydrolysis. Furthermore, a computational molecular docking over the GABAB receptor was performed to evaluate the interaction of each compound in the Baclofen binding site. With this information, we evaluated our compounds as GABAB agonists through a QSAR analysis. Finally, by means of molecular similarity analysis, and in silico ADME prediction, we support our three best compounds (8a–b, 8d) as potential GABAB receptor agonists.

Organics doi: 10.3390/org6010012

Authors: Mengying Kou Kanshe Li

A graft reaction of polyvinyl chloride (PVC) with furfural was conducted in a tetrahydrofuran solution. The resulting graft structure (FF-g-PVC) was characterized using UV spectroscopy, photoluminescence (PL), Fourier Transform Infrared (FTIR) spectroscopy, Raman spectroscopy, and proton nuclear magnetic resonance (1H NMR) spectroscopy. The grafting efficiency was determined through ultraviolet spectrophotometry. Thermal stability analysis via thermogravimetric (TG) testing revealed that furfural was successfully grafted onto the PVC chain. In a nitrogen atmosphere, the temperature of the maximum weight loss rate during the first stage of pyrolysis increased from 296.3 °C to 301.7 °C, while the activation energy for the second stage increased from 199.4 kJ/mol to 294.4 kJ/mol, indicating enhanced stability and delayed degradation of the PVC. Additionally, microwave irradiation markedly improved the graft reaction, achieving a grafting rate of 57.76‰ compared to only 1.808‰ with water bath heating. The optimal conditions were found to be a PVC/FF/Zn ratio of 1:1:0.9, with microwave irradiation for 20 min at 40 °C.

Organics doi: 10.3390/org6010011

Authors: Chamseddine Derabli Noureddine Rahim Roumaissa Djaba Sarra Aouidi Chawki Bensouici Stephanie Hesse Houssem Boulebd

Six secondary amine derivatives derived from salicylaldehyde (SA) were successfully synthesized in good to excellent yields and evaluated for their biological activities. The synthesized compounds exhibited remarkable antioxidant properties, as determined by ABTS and phenanthroline assays. Notably, compound 2 demonstrated an IC50 value of 5.14 ± 0.11 µM in the ABTS assay, approximately six to nine times lower than the standards BHT and BHA. In the phenanthroline assay, all compounds showed inhibition capacities five to ten times greater than BHT and comparable to BHA, with A0.5 values ranging from 9.42 to 31.73 µM. Among these, compound 5 displayed the lowest A0.5 value of 9.42 ± 1.02 µM. The anti-inflammatory activity, assessed through BSA denaturation, revealed that compounds 2 and 5 were the most promising, although their activity was moderate compared to the standard diclofenac. The insecticidal potential of the compounds was evaluated against the storage insect pest Tribolium castaneum. Among the tested derivatives, compounds 1 and 6 exhibited the highest efficacy, achieving maximum mortality rates of 73.31% and 76.67%, respectively, over a seven-day treatment period. Furthermore, the molecular geometry, electronic properties, and intramolecular interactions of all compounds were investigated using DFT calculations. Thermodynamic analyses of the antioxidant mechanisms suggested that the NH bond is the most likely site for free radical attacks. These findings underscore the significant biological potential of the synthesized salicylaldehyde-derived secondary amines.

Organics doi: 10.3390/org6010010

Authors: Valeria Gagliardi Jesús Castro Valentina Beghetto María Expósito Marco Bortoluzzi

The commercial flame-retardant 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) was almost quantitatively converted in sodium [2-(2-hydroxyphenyl)phenyl]phosphinate Na[OH-Ph-Ph-PHO2] and disodium 2-(2-phosphinatophenyl)benzen-1-olate Na2[O-Ph-Ph-PHO2] under mild reaction conditions and without the use of toxic reactants. The structure of Na[OH-Ph-Ph-PHO2] was determined by means of single-crystal X-ray diffraction. The inter- and intramolecular Na-O interactions generate a stair-like framework where the sodium cations are five-coordinated and exhibit a highly distorted coordination sphere. The two compounds are characterized by appreciable blue luminescence at the solid state upon excitation with UV light, attributed to S1→S0 decays on the basis of time-resolved measurements and computational calculations. The photoluminescence quantum yield is higher for Na2[O-Ph-Ph-PHO2], and the emission and excitation bands are shifted at longer wavelengths. The disodium salt showed affinity towards cellulose, and doped Na2[O-Ph-Ph-PHO2]@cellulose samples maintained emission features comparable to those of the pure compound. The nature of the interaction between cellulose and the emitting species was studied by means of periodic density functional theory calculations, that highlighted the role of the sodium cations.

Organics doi: 10.3390/org6010009

Authors: Madyan A. Yaseen Michael Oelgemöller

A series of photoacylations of 1,4-naphthoquinone with various aldehydes and using Pyrex-filtered UVB light was conducted under continuous-flow conditions. Acetone served as a triplet photosensitizer and convenient solvent that kept all materials in solution and could be easily removed. The corresponding acylated 1,4-naphthohydroquinone photoproducts were obtained in acceptable to excellent yields of 30–90% with residence times of just 70 min. The photoacylation process was successfully coupled with in-line oxidation to obtain acylated 1,4-naphthoquinones.

Organics doi: 10.3390/org6010008

Authors: Amanda Neves de Souza Adriano Monteiro de Castro Pimenta Rodrigo Moreira Verly

Bioactive peptides are promising therapeutic agents due to their antimicrobial and anticancer activities, although their lack of selectivity often limits clinical applications. This study demonstrates the optimal synthetic route for conjugating folic acid (FA) with the bioactive peptide Lunatin-1, aiming to improve selectivity for neoplastic cells. The synthesis combines solid-phase peptide synthesis (SPPS) and Cu(I)-catalyzed cycloaddition to link folic acid to Lunatin-1 via a triazole ring. Using the model tripeptide FIG-NH2, key intermediates and the final product were characterized by high-performance liquid chromatography (HPLC), mass spectrometry (MALDI-ToF), Fourier-transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR). Reaction yields and purity were optimized with FIG-NH2, providing a reproducible synthesis pathway. Additionally, the results confirmed successful conjugation, with the FA-Trz-Luna product exhibiting molecular integrity and structural stability, as validated by spectral analyses. This study highlights a potential synthesis route for peptide-folate conjugates to be used as selective and multifunctional therapeutic agents, laying the groundwork for biological evaluations of their cytotoxicity and antimicrobial properties.

Organics doi: 10.3390/org6010007

Authors: Aleksei E. Machulkin Stanislav A. Petrov Maria D. Kraynova Anastasiia S. Garanina Bayirta V. Egorova Roman V. Timoshenko Alexander N. Vaneev Alexander S. Erofeev Anna B. Priselkova Mikhail A. Kalinin Aleksei V. Medved′ko Stepan N. Kalmykov Elena K. Beloglazkina Sergey Z. Vatsadze

Nowadays, PSMA ligands are widely used for radiotheragnostic purposes in prostate cancer. The synthesis of a PSMA-Bisp conjugate was developed and realized with good yield (overall yield ~58% for the last two steps). All newly synthesized compounds were characterized by physicochemical methods: 1H and 13C NMR, HRMS, and LCMS (for biologically tested samples). Subsequently, Bisp1 (diacetate bispidine ligand), Bisp-alkyne (bifunctional derivative of Bisp1), and its conjugate PSMA-Bisp were labeled by 64Cu in mild conditions. In vitro studies of the labeled conjugate [64Cu]Cu-PSMA-Bisp have shown great stability in model solutions. Finally, [64Cu]Cu-PSMA-Bisp was compared to the well-known PSMA-617 conjugate labeled with 64Cu and they showed similar stability in excess bovine serum (BVS), and at the same time, labeling PSMA-Bisp with 64Cu is characterized by extremely high kinetics in mild conditions, while labeling PSMA-617 with 64Cu requires heating (90 °C). Thus, this conjugate can be incredibly promising for nuclear medicine.

Organics doi: 10.3390/org6010006

Authors: Pedro Freitas Dina Maciel Jolanta Jaśkowska Kamila Zeńczak-Tomera Yanbiao Zhou Guoyin Yin Ruilong Sheng

Developing new biomolecule–drug conjugates as prodrugs is a promising area for natural products and pharmaceutical chemistry. Herein, a cholesterol–doxorubicin (Chol-DOX) conjugate was synthesized using cholesteryl-4-nitrophenolate as a facile, stable, and controllable activated ester. This approach offers an alternative to the conventional HCl-emitting cholesteryl chloroformate method. Semi-empirical theoretical calculations showed that cholesteryl-4-nitrophenolate exhibits moderate reactivity, greater thermodynamic stability, a higher dipole moment, and a lower HOMO-LUMO energy gap compared to cholesteryl chloroformate, suggesting that cholesteryl-4-nitrophenolate could be used as a more controllable acylating agent. The structure of the synthesized Chol-DOX conjugate was characterized using NMR, MS, and FT-IR techniques. Biological properties of the Chol-DOX conjugate were analyzed with a comparison of theoretical and experimental data. This work provides a facile and controllable method to synthesize natural lipid–DOX prodrugs and offers an in-depth data analysis of the related biological properties.

Organics doi: 10.3390/org6010005

Authors: Maria S. Ledovskaya Vladimir V. Voronin Anna A. Reznichenko Ekaterina A. Reznichenko

In this work, we developed a highly efficient and versatile environmentally benign methodology for the vinylation of a broad scope of substances, including alcohols, thiols, and nitrogen compounds. The key advantage of the proposed method is the use of calcium carbide as a robust acetylene source in a stoichiometric ratio to the substrates. Lacking the requirement of acetylene excess, the developed protocol is safe, highly economic, and limits waste production. The procedure allows for a large variety of O-,S-,N-vinyl compounds to be synthesized in up to quantitative yields. Our methodology is scalable, allowing us to obtain vinyl derivatives in Gram-scale quantities. We also demonstrated the significant synthetic value of our approach by performing a label-economic synthesis of 13C2-labeled vinyl derivatives using calcium carbide-13C2. In our well-optimized process, the conversion of Ca13C2 reached 89%.

Organics doi: 10.3390/org6010004

Authors: Rostislava Angelova Georgi Stavrakov

Ferrocene is an organometallic compound that has attracted considerable scientific interest due to its unique properties, including low toxicity, excellent stability in aqueous and aerobic media, and high lipophilicity, which enhances membrane permeability. The ferrocene moiety has been effectively used as a bioisostere of phenyl rings and heteroaromatic groups in the structures of approved tyrosine kinase inhibitors and histone deacetylase inhibitors (HDACis). HDACis exert their cytotoxic effects by blocking cyclin/CDK complexes, causing cell cycle arrest, inducing apoptosis, inhibiting angiogenesis, and through non-histone-directed mechanisms. This mini-review summarizes the synthesis and biological evaluation of small libraries of compounds in which a ferrocenyl moiety is incorporated into the structure of suberoylanilide hydroxamic acid (SAHA) and a number of analogues. The influence of the organometallic function on the antiproliferative effect is investigated. Both docking analysis and in vitro studies confirm that the ferrocenyl-modified HDACis exhibit potent cytotoxicity and strong inhibitory activity against the various enzyme isoforms.

Organics doi: 10.3390/org6010003

Authors: Mukund Jha Dani Youssef Haley Sheehy Amitabh Jha

Heterocyclic compounds are the cornerstone for active pharmaceutical ingredients. Among heterocycles, isoindoline core occupies a special place, as ten commercial bioactive compounds/drugs contain this skeleton decorated with several functional groups required for optimal receptor binding. These drugs are employed for indications such as multiple myeloma, leukemia, inflammation, hypertension, edema, obesity, and insect control. This review presents the pharmacological activities, mechanisms of action, and chemical syntheses of these commercial bioactive molecules/drugs.

Organics doi: 10.3390/org6010002

Authors: Marija Popović-Nikolić Gordana Popović Slavica Oljačić Katarina Nikolić

The acid–base equilibria of cetirizine were investigated with and without the presence of differently charged micelle-forming surfactants (anionic, cationic, nonionic). The pKa values were potentiometrically determined at 25 °C and at a constant ionic strength (0.1 M NaCl). Experimental data were analyzed by applying the computer program Hyperquad 5.2.15. Based on a shift in the ionization constants (∆pKa) in micellar solutions against the pKa values determined in “pure” water under the same conditions, the effects of micelles on the protolytic equilibria of cetirizine were estimated. Applied micelles caused a shift in the protolytic equilibria of all cetirizine ionizable centers, with the piperazine function connected to aliphatic side moiety (∆pKa1 from −0.47 to +1.42), carboxyl group (∆pKa2 from −0.92 to +2.02), and piperazine nitrogen connected to phenyl rings (∆pKa3 from −2.01 to +2.19). Anionic SDS and nonionic Brij 35 micelles caused an increase in the pKa values of the ionizable centers of cetirizine, while a decrease in the pKa values was detected under the influence of cationic CTAB and nonionic TX-100 micelles. The change in the ionization pattern by micelles at pH values with biopharmaceutical significance provides indications of possible interactions of cetirizine with biomolecules of different charge and polarity under physiological conditions.

Organics doi: 10.3390/org6010001

Authors: Oussama Baaloudj Laura Scrano Sabino Aurelio Bufo Lee-Ann Sade Modley Filomena Lelario Angelica Rebecca Zizzamia Lucia Emanuele Monica Brienza

Heterocyclic pharmaceuticals are emerging contaminants due to their toxic, carcinogenic nature and detrimental impact on the natural ecosystem. These compounds pose a significant environmental concern given their widespread use in medical therapy, constituting over 90% of new medications. Their unique chemical structure contributes to their persistence in various environmental matrices, necessitating urgent measures to mitigate their risks. This review comprehensively examines the sources, environmental fate, toxicity, and long-term risks associated with heterocyclic pharmaceuticals, proposing potential remediation strategies. The article commences with an overview of the diverse types of heterocyclic pharmaceuticals and their applications, focusing on compounds containing heteroatoms such as nitrogen, oxygen, and sulfur. Subsequently, it explores the sources and pathways through which these pollutants enter the environment, including wastewater discharge, agricultural runoff, improper disposal, resistance to biodegradation, and bioaccumulation. The toxic effects and long-term consequences of exposure to heterocyclic pharmaceuticals are then discussed, encompassing neurotoxicity, genotoxicity, mutagenesis, cardiovascular and metabolic toxicity, carcinogenicity, and teratogenesis. Additionally, this review summarizes various remediation strategies and treatment solutions aimed at reducing the environmental impact of these compounds, drawing insights from the literature. The research concludes by identifying critical areas for future research, emphasizing the urgent need for more effective remediation strategies to address the growing concern posed by these emerging contaminants.

Organics doi: 10.3390/org5040035

Authors: László Kiss Péter Szabó

Various organic compounds susceptible to anodic polymerization were selected to study the effects of two solvents: acetic acid and ethyl acetate. Phenol and most of its derivatives, as well as resorcinol and 3,5-dihydroxybenzoic acid, exhibited typical electrode deactivation similar to other solvents; however, a continuous decrease in peak currents was not observed for 4-tert-butylphenols or salicylic aldehyde. Similar behavior was noted for monomers unrelated to phenols. In general, peaks were observed only for certain compounds and not in the initial voltammogram. Significant differences between the two solvents were observed in the subsequent voltammetric curves for some monomers. Microelectrode studies using 4-methoxyphenol as a model compound revealed notable differences between acetic acid and ethyl acetate in terms of curve shapes and the onset potentials of the plateaus. Plateau currents were used to estimate the solvent composition, demonstrating relatively high sensitivity to the acetic acid content.

Organics doi: 10.3390/org5040034

Authors: Aliya Yelshibay Sherif Dei Bukari Bakhytzhan Baptayev Mannix P. Balanay

The pursuit of sustainable energy sources has led to significant advances in solar cell technology, with conducting polymers (CPs) emerging as key innovations. This review examines how CPs improve the performance and versatility of three important types of solar cells: dye-sensitized solar cells (DSSCs), perovskite solar cells (PSCs), and organic solar cells (OSCs). Polymers such as polyaniline, polypyrrole, and poly(3,4-ethylenedioxythiophene) have shown significant potential to increase the efficiency of solar cells. In DSSCs, conducting polymers act as counter electrodes, electrolytes, and dyes, contributing to improved efficiency and stability. In PSCs, they serve as hole transport materials and electron transport materials that improve charge separation and reduce recombination losses. In OSCs, conducting polymers act as HTMs and active layers, significantly impacting device performance and enabling advances in both binary and ternary solar cell configurations. Recent research highlights the important role of conducting polymers in improving both the efficiency and stability of solar cells under different indoor and outdoor lighting conditions. Recent advances have led to impressive energy conversion efficiencies, particularly in low-light environments. This report also highlights the environmental and economic benefits associated with these materials. At the same time, it highlights the challenges associated with optimizing the materials, scalability, and ensuring long-term stability. Future research directions are outlined to overcome these obstacles and promote the commercial viability of next-generation solar technologies.

Organics doi: 10.3390/org5040033

Authors: Mirjana M. Radanović Ljiljana S. Vojinović-Ješić Niko S. Radulović Vidak N. Raičević Vukadin M. Leovac Marko V. Rodić

Due to the promising characteristics of aminoguanidine Schiff bases, ongoing research focuses on synthesizing and characterizing different compounds of this class to establish structure–property relationships. However, the pronounced alkalinity of the aminoguanidine residue makes isolating its Schiff bases in neutral form challenging. In the reaction of salicylidene-aminoguanidine ([HL]NO3) with a strong base (NaOH), the partially neutralized product of the formula [HL]NO3∙L·H2O was obtained in the form of single crystals. This compound could be considered a cocrystal in which protonated and neutral forms of the Schiff base coexist. Furthermore, the coordinating properties of [HL]NO3 towards zinc and organotin were investigated, and instead of the expected crystals of complex compounds, a novel polymorph of the ligand was obtained. Additionally, the reaction of [HL]NO3, NH4VO3 and salicylaldehyde was carried out to achieve the condensation of the free NH2-group in the aminoguanidinium fragment, targeting a vanadium(V) complex with tetradentate ligand. However, a purely organic compound containing three salicylaldehyde residues and two imine groups, i.e., C21H18N2O3, was isolated. All the obtained compounds were characterized by elemental and spectroscopic analysis, conductometry and SC-XRD analysis. The data were compared to those of similar structures, and the results provide further insight into the properties of these compounds and their future investigation for potential usage.

Organics doi: 10.3390/org5040032

Authors: Avital Shifrovitch Moran Madmon Tamar Shamai Yamin Avi Weissberg

We developed a selective technique to rapidly measure free chlorine, which is the sum of elemental chlorine (Cl2), hypochlorous acid (HOCl), and hypochlorite (OCl−) in water samples via an electrophilic aromatic substitution reaction hyphenated with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Sample preparation involved derivatization at 25 °C for 15 min with 3,4,5-trimethoxyphenylacetic acid (TMPAA) in an aqueous solution prior to analysis. Several parameters were evaluated to determine the optimized reaction and for the production of informative MS/MS spectrum of the derivatization product, 2-chloro-3,4,5-trimethoxyphenylacetic acid (Cl-TMPAA). The resulting Cl-TMPAA derivative displayed an informative ESI-MS/MS spectrum characterized by product ions at m/z 232.0142, 200.0245, and 185.0009 from the precursor ion at m/z 259.0379. The linear dynamic range of the method (0.1–10 µg/mL) was fitted to concentration levels relevant to forensic toxicology issues. Compared with other analytical techniques, this newly established LC-MS-based method demonstrated specificity, simplicity, and rapidity. This method enables the detection of free chlorine for forensic investigations in criminal cases.

Organics doi: 10.3390/org5040031

Authors: Natalia Agudelo-Ibañez Sergio Torres-Cortés Ericsson Coy-Barrera Ivon Buitrago Diego Quiroga

The synthesis of indole phytoalexin-like analogs related to alkyl (((1-(4-substitutedphenyl)-3-oxo-3-phenylpropyl)thio)carbonothioyl)-ʟ-tryptophanate 1a–d and the evaluation of their antifungal activity against the phytopathogen Fusarium oxysporum is reported. The target compounds were synthesized in the following two stages: (1) the initial esterification of ʟ-tryptophan, which reacted with trimethyl silane chloride and simple aliphatic alcohols (R = Me, Et) under microwave irradiation (MWI) at 100 °C to obtain the respective alkyl ester 2a–b; (2) the resulting mixture of ʟ-tryptophanates 2a–b with carbon disulfide and (E)-chalcone 3a–b under MWI at 50 °C during 60 min, followed by purification through classical column chromatography (55–76% yields). The products were obtained as mixtures of (S,R) and (S,S) diastereoisomers. An LC-DAD-MS analysis allowed us to establish the ratio of these diastereoisomers, and subsequent DFT/B3LYP-based computational calculations of the NMR 1H chemical shifts suggested that the major diastereoisomer involved an (S,R) absolute configuration, comprising more than 60% of the mixture. The compounds 1a–d were subjected to an antifungal activity test against the phytopathogen F. oxysporum using an amended medium-based assay. Compound series 1 showed inhibition percentages of 80% at the first concentration and IC50 values between 0.33 and 5.71 mM, demonstrating greater potential as antifungal agents compared to other ʟ-tryptophan derivatives like alkyl (2S)-3-(1H-indol-3-yl)-2-{[(1Z)-3-oxobut-1-en-1-yl]amino}propanoate, which presented lower inhibition percentages. In summary, phytoalexin analogs derived from ʟ-tryptophan and (E)-chalcones significantly inhibited the mycelial growth of Fusarium oxysporum, indicating their potential as effective antifungal agents.

Organics doi: 10.3390/org5040030

Authors: Mounir Cherfi Tarik Harit Malika Amanchar Ahlam Oulous Fouad Malek

Pyrazole and tetrazole are among the most important heterocyclic members of the azole family. Over the past decade, these N-heterocycles and their derivatives have demonstrated specific properties that give them potent applications in several fields such as pharmacology, technology, and agriculture. Combining these two azoles in single hybrid architecture has given rise to highly potent molecules in terms of efficacy and specificity, with enhanced and scalable properties. In this context, the present paper deals with the literature of the last 10 years describing the synthesis protocols for pyrazole-tetrazole-based molecules. Their biological activities as well as their energetic properties are also reported.

Organics doi: 10.3390/org5040029

Authors: Mohamed Anannaz Fatiha Tafraout Charaf Laghlimi Rachida Ouaabou Jalal Isaad

A simple approach was developed to efficiently graft diethylene triamine onto polystyrene waste using succinic anhydride as a tracer to remove nitrate anions from aqueous solutions. Infrared spectroscopic data showed characteristic signs at 3395 cm−1 and 1695 cm−1 corresponding to N-H and C=O (ester and amide), confirming the grafting of DETA onto PS. The zeta potential study showed that the PS-Succ-DETA adsorbent had a pHiep of 8.2, and its charge was positive when the pH was lower than the pHiep. Parameters affecting nitrate adsorption, such as dosage, initial concentration, pH, and contact time, were studied. The adsorption data corresponded well to the Langmuir isotherm with an R2 correlation coefficient of 0.998, and the adsorption capacity was found to be 195.65 mg/g. The adsorption kinetics of NO3− ions by PS-Succ-DETA corresponded perfectly to the PS-II model, with an R2 coefficient of 0.999. The negative value of ΔG (−10.02 kJ/mol), ΔH (−18.76 kJ/mol), and ΔS (−28.83 J/K/mol) indicates that NO3- adsorption is spontaneous exothermic and suggests a decrease in randomness at the solid-liquid interface during the adsorption. The mechanism of adsorption of nitrate ions onto PS-Succ-DETA occurs via electrostatic interactions and hydrogen bonds between the NO3− ions and the -NH2 and NH functions of PS-Succ-DETA.

Organics doi: 10.3390/org5040028

Authors: Ghazi Aman Nowsherwan Qasim Ali Umar Farooq Ali Muhammad Ahmad Mohsin Khan Syed Sajjad Hussain

This review provides a comprehensive overview of recent advancements in the synthesis, properties, and applications of organic materials in the optoelectronics sector. The study emphasizes the critical role of organic materials in the development of state-of-the-art optoelectronic devices such as organic solar cells, organic thin-film transistors, and OLEDs. The review further examines the structure, operational principles, and performance metrics of organic optoelectronic devices. Organic materials have emerged as promising candidates due to their low-cost production and potential for large-area or flexible substrate applications. Additionally, this review highlights the physical mechanisms governing the optoelectronic properties of high-performance organic materials, particularly photoinduced processes relevant to charge carrier photogeneration. It discusses the unique benefits of organic materials over traditional inorganic materials, including their light weight, simple processing, and flexibility. The report delves into the challenges related to stability, scalability, and performance, while highlighting the wide range of electronic properties exhibited by organic materials, which are critical for their performances in optoelectronic devices. Furthermore, it addresses the need for further research and development in this field to achieve consistent performance across different types of devices.

Organics doi: 10.3390/org5040027

Authors: Roman A. Irgashev Nikita A. Kazin

In this study, we developed an efficient strategy for constructing thieno[3,2-b]thiophene molecules from 3-nitrothiophenes, containing carbonyl fragments at the C-2 and C-5 atoms, by nucleophilic aromatic substitution of the nitro group in these substrates. It was shown that the reaction of 3-nitrothiophene-2,5-dicarboxylates with thiophenols, thioglycolates and 2-mercaptoacetone in the presence of K2CO3 proceeds rapidly via nucleophilic displacement of the nitro group with the formation of 3-sulfenylthiophene-2,5-dicarboxylates. Further treatment of the resulting thiophene-2,5-dicarboxylates, which have -SCH2CO2Alk or -SCH2COMe moiety at C-3 atom, with sodium alcoholates afford obtaining 2,3,5-trisubstituted thieno[3,2-b]thiophene derivatives according to the Dieckman condensation. In turn, the reaction of methyl 5-formyl-4-nitrothiophene-2-carboxylate with methyl thioglycolate or 2-mercaptoacetone in the presence of K2CO3 proceeds to directly form 2,5-disubstituted thieno[3,2-b]thiophenes.

Organics doi: 10.3390/org5040026

Authors: Jake Morrin Matthew Petitt Christopher Abelt

1,5-Acrylodan (1-(5-(dimethylamino)naphthalen-1-yl)prop-2-en-1-one) is prepared in six steps from 1-nitronaphthalene and 19% overall yield. The last three steps involve an aryllithium-directed nucleophilic addition, catalytic Kulinkovich cyclopropanation, and copper-catalyzed oxidative ring-opening to generate the acryloyl moiety. The fluorescent properties of 1,5-Acrylodan (AC) are reported. These include its solvatochromism and H-bond quenching by protic solvents. Its use as a bioconjugate sensor is demonstrated with Human Serum Albumin (HSA) through its covalent attachment to Human Serum Albumin (HSA) at the free cysteine-34 moiety. Unfolding studies with guanidinium chloride (GdmCl) and sodium dodecyl sulfate (SDS) are conducted to illustrate how the fluorophore responds to changes in both micropolarity and exposure to water.

Organics doi: 10.3390/org5040025

Authors: Rajendra Rohokale Rajendra Mane

l-(+)-Furanomycin 1 is a miniature antibacterial natural product that contains an α-amino acid core. This non-proteinogenic α-amino acid was first isolated in 1967 by Katagiri and co-workers from the fermentation broth of Streptomyces threomyceticus L-803 (ATCC 15795). It is a substrate of isoleucyl aminoacyl-tRNA synthetase that replaces isoleucine in the protein translation process and exhibits antibacterial properties in vitro. It effectively acts as an antibacterial agent against M. tuberculosis, E. coli, B. subtilis, and some Shigella and Salmonella bacterial species at concentrations as low as the micromolar range. Consequently, synthetic chemists have garnered considerable interest from their specific structure–activity profile, distinctive chemical compositions, and distinct biological profile. This review comprehensively describes cutting-edge synthetic methodologies for synthesizing furanomycin and its analogs reported to date. Therefore, this review will offer an initial perspective on synthesizing furanomycin and its customized compounds.

Organics doi: 10.3390/org5040024

Authors: Issam Ameziane El Hassani Khouloud Rouzi Anouar Ameziane El Hassani Khalid Karrouchi M’hammed Ansar

The triazole scaffold is a crucial component of heterocyclic chemistry, serving as a basic building block in organic synthesis, materials science, and medicinal chemistry. Triazole is a five-membered ring composed of three nitrogen atoms and two carbon atoms, and it exists in two isomeric forms: 1,2,3-triazole and 1,2,4-triazole. Compounds featuring the triazole ring are important heterocycles known for their diverse biological activities, including antimicrobial, antiproliferative, antimalarial, anticonvulsant, anti-inflammatory, antineoplastic, antiviral, analgesic, and anticancer properties. As a result, triazole derivatives have attracted significant attention from researchers. This review aims to provide a thorough overview of the published studies on the synthesis of triazole derivatives, highlighting various methods for obtaining the triazole moiety. These methods include classical approaches as well as microwave and ultrasound-assisted techniques.

Organics doi: 10.3390/org5040023

Authors: Laura D’Andrea Casper Steinmann

Pd EnCat™ 30 is a palladium catalyst broadly used in several hydrogenation and cross-coupling reactions. It is known for its numerous beneficial features, which include high-yielding performance, easy recovery, and reusability. However, the available data regarding its recyclability in Suzuki coupling reactions are limited to a few reaction cycles and, therefore, fail to explore its full potential. Our work focuses on investigating the extent of Pd EnCat™ 30 reusability in Suzuki cross-coupling reactions by measuring its performance according to isolated yields of product. Our findings demonstrate that Pd EnCat™ 30 can be reused over a minimum of 30 reaction cycles, which is advantageous in terms of cost reduction and more sustainable chemical production.

Organics doi: 10.3390/org5040022

Authors: Nuno Vale Raquel Ramos Inês Cruz Mariana Pereira

Photodynamic therapy (PDT) is a clinically approved therapeutic option for the treatment of various types of cancer. PDT calls for the application of photosensitizers (PSs) and photoactivation with a particular light wavelength while tissue oxygen is present. Anticancer efficacy depends on the combination of these three substrates leading to the generation of cytotoxic reactive oxygen species (ROS) that promote apoptosis, necrosis, and autophagy of cancer cells. However, one of the biggest problems with conventional PDT is the poor accumulation and targeting of PSs to tumor tissues, resulting in undesirable side effects and unfavorable therapeutic outcomes. To overcome this, new photosensitizers have been developed through bioconjugation and encapsulation with targeting molecules, such as peptides, allowing a better accumulation and targeting in tumor cells. Several studies have been conducted to test the efficacy of several peptide-conjugated photosensitizers and improve PDT efficacy. This review aims to present current insights into various types of peptide-conjugated photosensitizers, with the goal of enhancing cancer treatment efficacy, addressing the limitations of conventional PDT, and expanding potential applications in medicine.

Organics doi: 10.3390/org5040021

Authors: Alessia Catalano Annaluisa Mariconda Assunta D’Amato Domenico Iacopetta Jessica Ceramella Maria Marra Carmela Saturnino Maria Stefania Sinicropi Pasquale Longo

From Egyptian mummies to the Chanel N° 5 perfume, aldehydes have been used for a long time and continue to impact our senses in a wide range of perfumes, foods, and beverages. Aldehydes represent one of the categories of volatile organic compounds (VOCs), which are categorized as chemicals with boiling points up to 260 °C and can be found in indoor environments in the gaseous phase. Because of their potential or known hazardous properties for humans, the World Health Organization (WHO)-Europe provided some guidelines that may prevent several health risks. Indeed, some aldehydes, reported to be risky for humans, have been retired from the market, such as butylphenyl methylpropional (BMHCA). The purpose of this review is to summarize the most important aldehydes found indoors and outdoors and analyse in depth the toxicological aspects of these compounds, whose presence in perfumes is often underestimated. In addition, the ingredients’ synonyms that are reported in the literature for the same compound were unified in order to simplify their identification.

Organics doi: 10.3390/org5040020

Authors: Sanaz Gharehassanlou Hamzeh Kiyani

In this contribution, propylamine-functionalized cellulose (Cell-Pr-NH2) was employed as the catalyst in the three-component reaction between hydroxylamine hydrochloride and various types of aryl/heteroaryl aldehydes, ethyl acetoacetate/ethyl 4-chloroacetoacetate, or ethyl 3-oxohexanoate. The result of these experiments was the formation of 3,4-disubstituted isoxazol-5(4H)-one heterocycles. The desired five-membered heterocyclic compounds were obtained in good to high yields at room temperature. The investigation of different solvents led us to the conclusion that water is the best solvent to perform the current one-pot, three-component reactions. Attempts to find the optimal catalyst loading clearly showed that 14 mg of cell-Pr-NH2 seems to be sufficient to carry out the reactions. This method has highlighted some principles of green chemistry including less waste generation, atom economy, use of water as an environmentally friendly solvent, and energy saving. Purification without chromatographic methods, mild reaction conditions, simple work-up, low-cost reaction medium, saving time, and obtainable precursors are other notable features of this one-pot fashion.

Organics doi: 10.3390/org5040019

Authors: Alexandria Montavon M. Raquel Marchán-Rivadeneira Yong Han

Natural products have been a reliable source of drug compounds in medical research. Technological advances have led to the discovery and characterization of many compounds that were previously difficult to isolate. However, when searching for anticancer drugs, finding natural compounds that can bind to specific targets is a daunting task. Polycyclic tetramate macrolactams (PoTeMs), specifically, have been a source of antibiotics for a long time, though they possess certain cytotoxic properties that make them attractive candidates for anticancer drug discovery. This review covers the structural diversity and widespread availability of PoTeM compounds and the past research that demonstrates their effects on human cancer cell lines. Additionally, this review documents the known receptors and molecular mechanisms of these compounds in mammalian cells.

Organics doi: 10.3390/org5030018

Authors: Alina Artemenko Elza Sultanova Diana Mironova Aliya Akhatova Ekaterina Bondareva Daut Islamov Konstantin Usachev Svetlana Solovieva Vladimir Burilov Igor Antipin

Triazole derivatives of fluorescein-containing N,N-dimethylaminopropyl fragments and their ammonium salts were synthesized with yields of 74–85%. The resulting compounds exhibit fluorescent properties in the green region of the visible spectrum. The critical aggregation concentration (CAC) was estimated using a pyrene fluorescent probe corresponding to a range of 0.28–1.43 mM, and at concentrations above the CAC, the compounds form stable aggregates ranging from 165 to 202 nm. A relative quantum yield of 5–24% has been calculated based on fluorescence and UV spectra. The best value is shown by a derivative containing a tetradecyl substituent. When studying the photocatalytic properties of synthesized compounds through the reaction between N-substituted 1,2,3,4-tetrahydroisoquinoline and malonic ester, the mono-tetradecyl derivative demonstrated the best results. According to gas chromatography–mass spectrometry (GC-MS) data, the conversion of the initial heterocycle reached 95%. Therefore, these resulting compounds have the potential to act as an effective photocatalysts.

Organics doi: 10.3390/org5030017

Authors: Navneet Kaur Manvinder Kaur Harvinder Singh Sohal Haesook Han Pradip K. Bhowmik

Barbituric acid is a heterocyclic compound with various pharmacological and biological applications. This review paper provides a comprehensive overview of barbituric acid’s synthesis, reactions, and bio-applications, highlighting its multifaceted role in various fields. Many heterocyclic derivatives were formed based on barbituric acid, for instance, pyrano-fused pyrimidine derivatives, spiro-oxindole derivatives, chrome-based barbituric acid derivatives, and many more via the atom economic method, Michael addition reaction, Knoevenagel condensation reaction, etc. In the context of bio-applications, this review examines the production of a wide range of bioactive drugs like anti-histamine, anti-leprotic, sedative–hypnotic, anti-inflammatory, anti-urease, antiviral, anti-AIDS, antimicrobial, antioxidant, anticonvulsant, anesthetic agent, antitumor, and anticancer drugs using efficient multicomponent reactions. By showcasing the versatility and potential of this compound, it aims to inspire further research and innovation in the field, leading to the development of novel barbituric acid derivatives with enhanced properties and diverse applications, with coverage of the literature relevant up to 2024.

Organics doi: 10.3390/org5030016

Authors: Malika Amanchar Tarik Harit Mounir Cherfi Meryem Idrissi Yahyaoui Nour Elhouda Daoudi Abderrahmane Yahyi Abdeslam Asehraou Fouad Malek

The elaboration of a new family of tetrapodal molecules L1–L3 bearing two pyrazole–tetrazole units is presented. The structure assigned to such molecules was verified by various techniques, including FTIR, NMR, HRMS and elemental analysis. The ability of these tetrapods to inhibit the growth of four fungal strains was examined, and the obtained results showed that they have some antifungal potency in the range of 12–16 mm. The alpha-amylase inhibition activity of these molecules was also evaluated. The obtained IC50 values (1.34 × 10−1–1.2 × 10−2 mg/mL) demonstrated that all compounds are potent enough to inhibit this enzyme much better than the positive control acarbose (2.6 × 10−1 mg/mL). A docking study on the porcine alpha-amylase was performed, and the results were in good correlation with the experimental results.

Organics doi: 10.3390/org5030015

Authors: Lucia Emanuele Maurizio D’Auria

The art of dyeing textiles has a long history, as natural dyes have been used since prehistoric times. With the development of synthetic dyes in the 19th century, the focus shifted from natural to synthetic dyes due to their superior properties. Recently, however, interest in natural dyes has increased again due to environmental and health concerns. Among industrial dyes, heterocyclic dyes, especially azo dyes, are of great importance due to their color brilliance and fastness. This review examines the synthesis, application, and analysis of azo dyes, especially heterocyclic dyes. It deals with monoazo, diazo, and polyazo dyes and highlights their structures, synthesis methods, and fastness properties. In addition, the ecological impact of azo dyes and practical solutions for their synthesis and application are discussed.

Organics doi: 10.3390/org5030014

Authors: Thomas C. Nugent Nilesh N. Shitole

A series of new aromatic substituted indanone and indanol building blocks have been prepared and are anticipated to aid future drug discovery studies. In total, seven compounds (7, 12–17) are expounded on, and all have been fully characterized. In doing so, we have shown multiple examples of highly chemoselective reactions. One example employed an adaptation of Fujioka’s chemoselective reduction methodology, allowing an ester to be reduced in the presence of a ketone. In another example, an uncommon benzylic methyl group to aldehyde oxidation was demonstrated for two different compounds. These and other chemoselective interconversions allowed us to identify compound (12) as a remarkably flexible springboard for accessing a diverse array of indan-based building blocks (13–17).

Organics doi: 10.3390/org5030013

Authors: Taku Shoji Daichi Ando Masayuki Iwabuchi Tetsuo Okujima Ryuta Sekiguchi Shunji Ito

Synthesis of 3,8-diaryl-2H-cyclohepta[b]furan-2-ones was accomplished by the one-pot procedure involving sequential iodation and Suzuki–Miyaura coupling reactions. The optical and structural characteristics of 3,8-diaryl-2H-cyclohepta[b]furan-2-ones prepared were scrutinized using UV/Vis spectroscopy, theoretical calculations, and single-crystal X-ray crystallography. The redox properties of the compounds were also evaluated through cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The findings reveal that the introduction of aryl groups at both the 3- and 8-positions significantly influences the electronic properties of the CHFs, resulting in distinct optical and electrochemical characteristics.

Organics doi: 10.3390/org5030012

Authors: Ilaria Caivano Alessandro Santarsiere Mario Amati Paolo Convertini Maria Funicello Paolo Lupattelli Lucia Chiummiento Anna Santarsiero

Permethylated anigopreissin A (PAA), a fully protected form of the natural anigopreissin A, was found in our previous study to be active against several cancer cells, up to IC50 0.24 μM for HepG2 cells. Herein, a total of thirteen PAA analogues with variations in the number, position of substituents and unsaturation were synthesised starting from a common precursor, and their ability to induce cell growth inhibition was tested. By comparing the antiproliferative effect of the analogues with PAA and with the help of computational studies, we have gained valuable insights into both the biological activity and structure of this natural class of compounds. Indeed, we discovered the importance of the C-3 ring in modulating the biological activity of PAA, as well as the crucial role of the trans configuration of the styryl double bond and the significance of substitutions on the other parts of the molecule.

Organics doi: 10.3390/org5030011

Authors: Dandan Jiang Jun Xiao Yingzhen Zhang Kunming Liu Juanhua Li Jinbiao Liu

In light of the small ring strain of five/six-membered cyclic ethers, constructing complex molecules via ring-opening reactions has consistently been a highly challenging topic in organic synthesis. Induced by Lewis acids, the charge redistribution in cyclic ethers forms oxonium ylide intermediates, thereby activating the C–O bond and subsequently facilitating nucleophilic attack for ring opening. In recent years, a variety of novel Lewis acids, encompassing those with new metal centers and frustrated Lewis pairs (FLPs), have been effectively utilized to induce the formation of oxonium ylides, offering a diverse array of methods for the ring opening of five/six-membered cyclic ethers. This review conveys the extensive application advancements of diverse Lewis acid types for cyclic ether ring-opening reactions over the past two decades, originating from the perspective of the classification of Lewis acids. Furthermore, the substrate applicability and chemical transformation efficiency of these Lewis acids in the ring-opening reactions of cyclic ethers have also been discussed herein.

Organics doi: 10.3390/org5030010

Authors: Gary W. Breton Jazmine V. Ridlehoover

Bridgehead alkenes are polycyclic molecules bearing at least one C=C bond that includes a bridgehead carbon atom. For small bicyclic systems, these bonds are highly strained due to geometric constraints placed on the sp2 hybridized carbon atoms. These small, strained molecules have been termed “anti-Bredt” alkenes. β-halo carbanions have served as convenient precursors to bridgehead alkenes in experimental studies. We observed that upon attempted computational geometric optimizations (ωB97X-D/aug-cc-pVDZ) of the precursors, spontaneous elimination of the halide occurs along with formation of the anti-Bredt alkene in many cases. Such computational eliminations were shown to faithfully mimic experimentally obtained results. Computational elimination was not observed for [1.1.1] or [2.1.1] frameworks, in agreement with predictions that these bridgehead alkenes are too strained to be formed. However, computational elimination from the [2.2.1] framework was observed to form 1-norbornene, a compound suggested in experimental work to be a reactive intermediate. Similarly, [3.1.1] frameworks and higher led to eliminations upon computational geometric optimization, in agreement with experimental findings. Natural bond order (NBO) calculations of the starting geometries proved to be excellent predictors as to whether elimination would take place. Those precursor compounds exhibiting delocalization energies in the order of 10 kcal/mol between the lone-pair electrons of the carbon atom and σ*C-Br were generally found to undergo elimination. Thus, computational optimization of β-halo substituted bicyclic precursor anions can be used to predict whether strained anti-Bredt alkenes are likely to be formed, thereby saving valuable time and costs in the experimental lab.

Organics doi: 10.3390/org5030009

Authors: Mario Orena Samuele Rinaldi

This review deals with the functionalization of double bonds carried out in the presence of a chiral catalyst exploiting the intramolecular attack to haliranium ions by nucleophilic nitrogen of amides or carbamates prepared from achiral aminoalkenes, and the C–N bonds formation leads to highly enantioenriched nonaromatic heterocycles. A range of protocols are reported, emphasizing the synthesis of many natural and biologically active products of pharmacological interest prepared according to this methodology.

Organics doi: 10.3390/org5020008

Authors: Gleiston G. Dias Francielly T. Souto

Three decades after A. P. de Silva’s seminal paper introduced the concept of logic gates at the molecular level, the field of molecular logic gates (MLGs) has witnessed significant advancements. MLGs are devices designed to perform logical operations, utilizing one or more physical or chemical stimulus signals (inputs) to generate an output response. Notably, MLGs have found diverse applications, with optical detection of analytes emerging as a notable evolution of traditional chemosensors. Organic synthesis methods are pivotal in crafting molecular architectures tailored as optical devices capable of analyte detection through logical functions. This review delves into the fundamental aspects and physical–chemical properties of MLGs, with a particular emphasis on synthetic strategies driving their design.

Organics doi: 10.3390/org5020007

Authors: Tomasz K. Olszewski

Organophosphorus compounds, due to their interesting physicochemical properties, have found wide applications in many important areas of the chemical industry, such as the synthesis of utility chemicals [...]

Organics doi: 10.3390/org5020006

Authors: Włodzimierz Buchowicz Mariola Koszytkowska-Stawińska

Nucleoside analogs (NAs) have been extensively examined as plausible antiviral agents in recent years, in particular since the outbreak of the global pandemic of COVID-19 in 2019. In this review, the structures and antiviral properties of over 450 NAs are collected according to the type of virus, namely SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-229E, and HCoV-NL63. The activity of the NAs against HCoV-related enzymes is also presented. Selected studies dealing with the mode of action of the NAs are discussed in detail. The repurposing of known NAs appears to be the most extensively investigated scientific approach towards efficacious anti-HCoV agents. The recently reported de novo-designed NAs seem to open up additional approaches to new drug candidates.

Organics doi: 10.3390/org5020005

Authors: Lingxia Chen Junyu Li Ke Ni Xinshu Qin Lijun Wang Jiaman Hou Chao Wang Xuan Li Minlong Wang Jie An

Polyether amines are versatile compounds characterized by a flexible structure, consisting of polyoxypropylene and polyoxyethylene as the backbone, with amine groups at each end. They have widespread applications in various industrial processes and daily life. Despite their versatility, the utilization of polyether amines as base catalysts is rare. In this study, one kind of three-arm polyether amine 1 was employed as an environmentally friendly, cost-effective catalyst for the aerobic oxidation of thiophenols, leading to the synthesis of disulfides. The oxidative coupling of thiols serves as a fundamental pathway for the production of disulfides, which are vital in both chemical and biological processes. In contrast to known methods for thiol oxidation, this polyether amine-based catalytic process eliminates the need for expensive stoichiometric oxidants and minimizes the formation of over-oxidized by-products. Using a mere 0.5 mol % of the polyether amine 1 as the catalyst, a remarkable > 96% yield was achieved for all 16 tested substrates, encompassing a diverse range of functional groups, under the catalytic aerobic oxidation conditions. Furthermore, it is noteworthy that over 90% of the polyether amine catalyst can be efficiently recovered for reuse without loss of activity, making this a sustainable and cost-effective catalytic approach.