Chemistry, Volume 6, Issue 4 (August 2024) – 20 articles

A pyridine–tricarboxylic acid, 4-(6-carboxy-pyridin-3-yl)-isophthalic acid (H₃cpia), was used as a versatile building block to synthesize three novel coordination polymers under hydrothermal conditions and formulated as [Mn₈(μ₃-Hcpia)₂ (μ₆-cpia)₄(Hbiim)₂(H₂O)₆]_n·6nH₂O (1), [Cu₃(μ₄-cpia)₂(bipy)₂(H₂O)₂]_n·4nH₂O (2), and [Ni₃(μ₃-cpia)₂(dpe)₃(H₂O)₂]_n·4nH₂O (3). Three supporting ligands, 2,2′-biimidazole (H₂biim), 2,2′-bipyridine (bipy), and 1,2-di(4-pyridyl)ethane (dpe), were used in the synthesis. The structures of the studied products 1–3 varied significantly, ranging from a 1D chain (2) to 2D sheets (1 and 3). Furthermore, these compounds were evaluated as heterogeneous catalysts for the Henry reaction, achieving high product yields under optimized conditions. In addition, we investigated various reaction parameters and substrate scopes, and assessed the feasibility of catalyst recycling. This thorough investigation’s results highlight the versatility of H₃cpia as a tricarboxylate building block in the formation of functional coordination polymers. Full article

A novel dicoumarol-based copolyester was synthesized via a one-step polycondensation reaction using titanium tetraisopropoxide (TTIP) as a catalyst. The copolyester was characterized using Fourier transform infrared spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR) spectroscopy (1H and 13C), and Differential Scanning Calorimetry (DSC). Scanning electron microscopy (SEM) was used to examine the surface morphology before and after degradation. The synthesized copolyester exhibited toxicity against MCF-7 breast cancer cells, with an IC₅₀ value of 62.5 μg/mL, and demonstrated potential as a drug carrier with a consistent drug-release rate. The combination of dicoumarol, itaconic acid, and 1,12-dodecanediol in the copolyester enhances its biomedical capabilities, with dicoumarol providing anticancer properties, itaconic acid offering biocompatibility and mechanical stability, and 1,12-dodecanediol ensuring structural integrity and responsiveness. This study presents the first example of a dicoumarol-substituted copolyester, which was thoroughly characterized and shown to have promising biocompatibility for targeted anticancer therapy. The synthesis of this novel copolyester from renewable sources highlights the growing interest in sustainable materials for pharmaceutical and biomedical applications, particularly in drug delivery and tissue engineering for cancer treatment. Full article

Organometallic ruthenium complexes with p-cymene = 1-methyl-4-(1-methylethyl)-benzene and N^N = bidentate polypyridyl ligands constitute interesting candidates with biological and catalytic properties. Towards this aim, we have synthesized four ruthenium(II)–arene complexes of the type [Ru(η⁶-p-cymene)(N^N)Cl][X] (N^N = Br-Qpy = 6-bromo-4-phenyl-2-pyridin-2-yl-quinoline, X = Cl⁻ (1a); PF₆⁻ (1b); N^N = OH-Ph-Qpy = 4-(4-phenyl-2-(pyridin-2-yl)quinolin-6-yl)phenol, X = Cl⁻ (2a); PF₆⁻ (2b)). This is the first report of ruthenium(II) p-cymene complexes incorporating substituted pyridine–quinoline ligands, with –Br and –C₆H₄OH groups in the 6-position of quinoline. We also refer to the cytotoxicity of the ligands and their possible effect of modulating the activity of the ruthenium(II) complexes. These were characterized by a combination of spectroscopic methods (ATR-IR, UV–Vis, multinuclear NMR), elemental analysis, and conductivity measurements. The solid-state structure of 2b, determined by single-crystal X-ray diffraction, reveals a three-legged piano-stool geometry. The in vitro cytotoxic activities of the new complexes were evaluated in HEK293T (human embryonic kidney cells) and in HeLa cells (cervical cancer cells), via the MTT assay. Poor in vitro anticancer activities were observed for the HeLa cancer cell line, with 2a being the most potent (IC₅₀ = 75 μΜ). The cytotoxicity of Br-Qpy in HEK293T is comparable to that of cisplatin. Both complexes 1a and 1b successfully catalyze the transfer hydrogenation of benzophenone to benzhydrol by 2-propanol at 82 °C. The catalytic performance of 1a in the ratio of S:Cat:B = 400:1:40 (S = substrate, Cat = catalyst, B = base = KOiPr) leads to a conversion of 94%, within 3 h of reaction. Presumably, catalytic transformation takes place via ruthenium(II) hydride species being the active catalyst. Full article

Three amidine-based ligands were used in the crystal design of a series of mononuclear Zn(II) complexes. Interaction of zinc chloride, ZnCl₂, with N-2-pyridylimidoyl-2-pyridylamidine (Py₂ImAm) resulted in complexes [Zn(Py₂ImAm)₂] (1) and [ZnCl₂(Py₂ImAm)] (2). In [Zn(Py₂ImAm)₂] (1, monoclinic, P2₁/c), the metal ion was coordinated with the bidentate pocket of the anionic form of Py₂ImAm, while in [ZnCl₂(Py₂ImAm)] (2, monoclinic, P2₁/n), the tridentate coordination to a neutral Py₂ImAm was completed by two chloride anions. This structural variation was achieved by a pH-controlling strategy using the weak base triethylamine (TEA). Otherwise, three ionic complexes were obtained with 2-amidinopyridine (PyAm) and Zinc(II), [ZnCl(PyAm)₂]Cl (3, triclinic, P-1), [ZnCl(PyAm)₂]₂[ZnCl₄]·C₂H₅OH (4, monoclinic, P2₁/n), and [ZnCl(PyAm)₂]₂Cl·CH₃OH (5, triclinic, P-1). They comprised the same [ZnCl(PyAm)₂]⁺ monocation with a butterfly-like shape provided by the bidentate chelate coordination of two PyAm neutral entities and a chloride ligand. In a similar butterfly shape, ionic complex [ZnCl(PmAm)₂]₂[ZnCl₄] (6, monoclinic, C2/c) comprised the mononuclear [ZnCl(PmAm)₂]⁺ cations with two bidentate chelate-coordinated 2-amidinopyrimidine (PmAm) as neutral ligands. The Zn(II) pentacoordinated arrangement in 3–6 was variable, from square pyramidal to trigonal bipyramidal. The reported compounds’ synthetic protocols, crystal structures and photoluminescence properties are discussed. Full article

A set of Pd-containing composites was prepared by the deposition of Pd on the following carriers: polyaniline (PANI); PANI doped by H₂SO₄; Norit GSX activated carbon or Aerosil (SiO₂) coated by PANI or by H₂SO₄-doped PANI; PANI after thermal treatment at 300 °C in an atmosphere of H₂. One sample was also prepared by the in situ polymerization of aniline in the presence of Pd²⁺· The decomposition of Pd was carried out via deposition from the solutions of Pd²⁺ salts or decomposition of Pd⁰ complex Pd₂(dba)₃, where dba is dibenzylideneacetone. The composites were studied by powder X-ray diffraction, transmission electron microscopy, IR and Raman spectroscopy. The hydrogenation of quinoline in the presence of composites was carried out; the catalytic performance of the composites was evaluated by the yield of 1,2,3,4-tetrahydroquinoline. It was found that the doping of PANI by H₂SO₄, inclusion of Norit GSX activated carbon as a component of the carrier or thermal treatment of PANI prior to the deposition of Pd led to significant increase in the catalytic performance of the composites in the hydrogenation of quinoline. Full article

“Are we asking the right questions?” seems cliché, but for ChatGPT, it is a pivotal tool to ensure the accuracy of responses. While ChatGPT-3.5’s training on the vast database promises to revolutionize STEM education and research, this investigation shows the importance of precise communication and prompt engineering in guiding ChatGPT-3.5 toward reliable and accurate responses, particularly in chemistry. For instance, emphasizing context, clearly defining symbols, and focusing on field-specific instructions can dramatically improve its performance. Furthermore, avoiding open-ended prompts and strategically using repetition can further enhance its accuracy. The iterative prompt design, demonstrated through a series of adjustments, illustrates how seemingly minor refinements, such as substituting “least” for “lowest”, profoundly impact the output. This study highlights the essential role of human oversight, including the construction of well-crafted prompts, in guarding reliable information and nurturing a productive “Human–AI” (HAI) partnership. Full article

Carvone belongs to the chemical family of terpenoids and is the main component of various plant oils. Carvone and its hydrogenated products are used in the flavouring and food industries. A quantitative thermodynamic analysis of the general network of carvone hydrogenation reactions was performed based on the thermochemical properties of the starting carvone and all possible intermediates and end products. The enthalpies of vaporisation, enthalpies of formation, entropies and heat capacities of the reactants were determined by complementary measurements and a combination of empirical, theoretical and quantum chemical methods. The energetics and entropy change in the hydrogenation and isomerisation reactions that take place during the conversion of carvone were derived, and the Gibbs energies of the reactions were estimated. It was shown that negative Gibbs energies are recorded for all reactions that may occur during the hydrogenation of carvone, although these differ significantly in magnitude. This means that all these reactions are thermodynamically feasible in a wide range from ambient temperature to elevated temperatures. Therefore, all these reactions definitely take place under kinetic and not thermodynamic control. Nevertheless, the numerical Gibbs energy values can help to establish the chemoselectivity of catalysts used to convert carvone to either carvacarol or to dihydro- and terahydrocarvone, either in carvotanacetone or carveol. Full article

Eleven new differently substituted N,7-diphenylpyrimido [4,5-d]pyrimidin-4-amines 4a–k were synthesized from readily available reagents in a simple and inexpensive two-step procedure with yields up to 57%. Neuroprotective analysis against H₂O₂ and analysis using ORAC assays identified compounds 4g, 4i and 4j as promising antioxidant compounds. These compounds also showed potent inhibition of Aβ_1–42 self-aggregation, and suitable physicochemical properties predicted by Datawarior software V6.1.0, this biological activity and physicochemical property being of great interest for pathologies linked to oxidative stress, such as Alzheimer’s disease. Full article

Aaptamine (8,9-dimethoxy-1H-benzo[de][1,6]naphthyridine), an alkaloid obtained from marine sponges of the genus Aaptos (Demospongiae, Suberitida, Suberitidae), has attracted significant attention as a promising scaffold for the development of antioxidant, antibacterial, and anticancer agents. This review offers an extensive overview of updated research on aaptamine, focusing on its multifaceted pharmacological properties. The antioxidant potential of aaptamine reflects its potential ability for use in the DPPH free radical scavenging assay, for suppressing ROS, and subsequently deactivating the MAPK and AP-1 signaling pathway. Moreover, it demonstrates notable antibacterial activity against pathogenic bacteria, including mycobacterial active and dormant states, making it a potential candidate for combating bacterial infections. Additionally, aaptamine shows promising anticancer activity by inhibiting cancer cell proliferation, apoptosis induction, and suppressing tumor growth through various signaling pathways, including the regulation of PTEN/PI3K/Akt and CDK2/4, and the regulation of cyclin D1/E in cell cycle arrest. The unique chemical structure of aaptamine offers opportunities for structural modifications aimed at enhancing its antioxidant, antibacterial, and anticancer activities. The exploration of aaptamine as a scaffold in the development of novel therapeutic agents offers great promise for addressing various challenges associated with oxidative stress, bacterial infections, and cancer. This article underscores the potential of aaptamine as a valuable marine-derived scaffold in the fields of antioxidant, antibacterial, and anticancer therapy. Full article

Two series of lactone-terminated alkanethiol adsorbates with five- and six-membered lactone groups, γ-COCnSH and δ-COCnSH (n = 11, 12), were synthesized and employed to create nanoscale self-assembled monolayers (SAMs) on gold substrates to mimic the properties of commercially available poly(lactic-co-glycolic acid) (PLGA) and poly(glycolic acid) (PGA) surfaces. ¹H and ¹³C nuclear magnetic resonance (NMR) were employed to characterize the adsorbate molecules. The thicknesses of the corresponding self-assembled monolayers (SAMs) were evaluated by ellipsometry. The conformational characteristics of the SAMs were analyzed using polarization modulation infrared reflection adsorption spectroscopy (PM-IRRAS), with a focus on the C-H antisymmetric stretching vibrations of the alkyl spacers. To evaluate the packing densities of the monolayers, X-ray photoelectron spectroscopy (XPS) measurements were performed. Separately, contact angle measurements provided insights into the wettability of the surfaces. Remarkably, the contact angle data across a broad range of probe liquids for the γ-COC11SH and γ-COC12SH SAMs were consistently similar to each other and to the contact angle values of the PLGA surface, rather than to PGA. This finding suggests that the lactone-terminated SAMs investigated in this study effectively mimic nanoscale polyester surfaces, enabling the exploration of interfacial properties of polyesters in the absence of swelling and/or surface reconstruction phenomena. Full article

Sulfated polysaccharides have a variety of important biologically active properties, such as anticoagulant, hypolipidemic, antiviral activity, the ability to be a means of targeted drug delivery and to improve the water solubility of certain drugs. Initial and sulfated polysaccharides’ biological activity depends on the method of their preparation, composition and structure. Currently, there is an extensive body of literature data on methods for the sulfation of various natural polysaccharides. However, modern reviews on this topic mainly focus on the biological activity and application of sulfated polymers, rather than on synthesis methods. The latest comprehensive review on methods for the synthesis of sulfated polysaccharides was performed by Caputo in 2019. To further study this area, you need to know the latest trends in this topic. Based on this, we decided to create a new, up-to-date review covering most of the existing methods for the synthesis of sulfated polysaccharides. This work examined methods for the synthesis of biologically active polysaccharide sulfates and their effect on polymer characteristics, as well as the advantages and disadvantages of each method. Traditional methods for sulfating polysaccharides were reviewed such as using a complex of sulfur trioxide with pyridine, and new methods based on the use of toxic free and corrosive free reagents. Some data on the biological activity of the obtained polysaccharides are considered. Full article

Transition metal complexes of nickel(II) with 5–bromo–N–(8–quinolyl)salicylaldimine (HqsalBr, HL¹); [Ni(qsalBr)₂] (1) and 3,5–dibromo–N–(8–quinolyl)salicylaldimine (HqsalBr₂, HL²); [Ni(qsalBr₂)₂] (3) including zinc(II) complex with HL¹, [Zn(qsalBr)₂] (2), have been synthesized and successfully characterized using various techniques, namely IR, NMR, mass spectrometry, thermogravimetric analysis (TGA), and single crystal X–ray crystallography. DFT calculations were employed to examine the structural and electronic parameters of the complexes at their optimized geometries. The complexes showed strong DNA-binding activities, assessed by UV-Vis and fluorescence spectroscopy, primarily through intercalation. Molecular docking investigations were carried out to provide profound insights into the interaction mechanisms of these complexes with DNA and lung cancer cells. These computational studies revealed that [Ni(qsalBr₂)₂] (3) exhibits the most favorable negative binding energies, −9.1 kcal/mol with DNA and −9.3 kcal/mol with cancer cells, facilitated by hydrogen bonding and hydrophobic interactions. Furthermore, the in vitro anticancer activity was evaluated against the A549 human lung adenocarcinoma cell line, with [Zn(qsalBr)₂] (2) exhibiting the highest potency against this cancer cell line. Full article

Carboxylato-bridged dinuclear and tetranuclear Mn(II) complexes 1–3 with ditopic ligands featuring two N₃-terminal coordination sites connected by hexyl (tphn), octyl (tpon), and p-xylyl (tpxn) linkers have been synthesized and characterized through X-ray single-crystal structure analyses, infrared spectroscopy, and elemental analyses. Complex 1 is a μ-fluorido-bis-μ-acetato dinuclear Mn(II) complex where the ligand tphn coordinates to both terminal sides of a dinuclear Mn unit. In contrast, complexes 2 and 3 are tetranuclear Mn(II) complexes with a macrocyclic structure, in which two dinuclear Mn units are linked by ligands tpon or tpxn. The redox behaviors of 1 and 2 were elucidated by cyclic voltammetry, revealing two metal-centered redox processes corresponding to Mn₂(II,II)/Mn₂(II,III) and Mn₂(II,III)/Mn₂(III,III). Full article

Natural curcumin is composed of three curcuminoids, namely curcumin (CUR), deme-thoxycurcumin (DMC) and bis-demethoxycurcumin (BDMC). These compounds are utilized in various biophotonics applications, including photodynamic therapy (PDT). This work aimed to evaluate the photodynamic action (alternative to antibiotics) of synthetic curcuminoids against Staphylococcus aureus. Herein, we evaluated an optimal proportion of the three curcuminoids mixed in solution to improve photoinactivation effects. Therefore, a set of computational calculations was carried out to understand the photodynamic action (stability and mechanism) of curcuminoids. Regarding computational analysis, the curcuminoid molecules were optimized using DFT with the hybrid exchange–correlation functional M06-2X, which includes long-range correction, and the 6-311++G(d,p) basis set. DMC and BDMC were more effective as photosensitizers than curcumin at a very low concentration of 0.75 µM, inactivating more than five orders of magnitude of S. aureus. Theoretical UV-vis absorption spectra showed that at maximum absorption wavelengths, electronic transitions of the π→π* type originated from H→L excitations. The BDMC was more stable than the other two curcuminoids after photobleaching, and the fluorescence emission was also higher, which could lead to its usage as a fluorescence dye to track bacteria. In fact, the results of electronic structure calculations proved that the stability order of curcuminoids is CUR < DMC < BDMC. The mixture of synthetic curcuminoids was more effective in the inactivation of S. aureus compared to curcumin by itself; for all proposed mixtures, an equal or superior reduction was achieved. Full article

Azide-containing compounds, organic azides, showcases a variety of reactivities, making them highly convenient and chameleonic intermediates. An indoline derivative has been proven to be of great significance in drug discovery due to its sp³-rich property. In this context, it is interesting to perform such vigorous azidation on medicinal-relevant indoles/indolines, resulting in the production of sp³-rich azidoindolines. The potential biological activity, in combination with the sp³-rich indoline bearing the azido moiety, makes azidoindolines an attractive synthetic target for medicinal and synthetic chemists. This review describes recent advances in the synthesis and application of azidoindolines: (1) iodine-mediated azidations, (2) metal-catalyzed azidations, (3) electrochemical azidations, (4) photochemical azidations, (5) azidation using a combination of an oxidant and an azide source, and (6) nucleophilic azidation. Full article

Dicerothamnus rhinocerotis (L.f.) Koekemoer, also known as rhinoceros bush and previously called Elytropappus rhinocerotis (L.f.) Less., is from the Asteraceae plant family. The plant is traditionally used to treat indigestion, stomach ulcers, influenza, and diarrhea. This study was aimed at investigating the phytochemistry, anti-glucosidase, anti-amylase, and anti-tyrosinase effects of D. rhinocerotis as research in this area is limited. The air-dried plant materials were macerated in 80% methanol (MeOH) and fractionated between hexane, dichloromethane (DCM), ethyl acetate (EtOAc), and butanol (BuOH). Column chromatography on silica gel was employed for the isolation of the compounds. A total of six compounds (1–6) were isolated from the fractions viz. acacetin (1), 15-hydroxy-cis-clerodan-3-ene-18-oic-acid (2), acacetin-7-glucoside (3), pinitol (4), apigenin (5), and β-sitosterol-3-O-glycoside (6). Compounds 2–4 and 6 are reported for the first time from this plant. Among the different fractions, the BuOH and EtOAc fractions had strong tyrosinase inhibitory activities with IC₅₀ values of 13.7 ± 1.71 and 11.6 ± 2.68 µg/mL, respectively, while among the isolated compounds, apigenin (5) had the strongest inhibitory activity, with an IC₅₀ of 14.58 µM, which competes favorably with Kojic acid (17.26 µM). The anti-glucosidase assay showed good activity in three of the fractions and compound 5, while the anti-amylase assays did not show significant inhibition activity. Full article

We explore the phase behavior of lipid bilayers containing SOPC (1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine) with various molar concentrations (0 mol%, 10 mol% and 30 mol%) of cholesterol. To this end, we performed extensive atomistic molecular dynamics simulations in conjunction with the Slipids force field with optimized parameters for the headgroups of phospholipids. We computed thermodynamic and structural quantities describing the ordering of the tails, the mobility of the heads and the arrangement of the lipids in the bilayers. We analyzed the behavior of the named quantities over the temperature range between 271 K and 283 K, where the experimentally determined melting temperature, $T_m=279$ K, lies, as well as at 400 K, which is used as a reference temperature. The obtained results are compared to available experimental data along with the outcome from molecular dynamics simulations of similar phospholipids containing different amounts of cholesterol. In the temperature interval of interest, we found evidence of the occurrence of a thermal-driven phase transition (melting) in both the pure system and the one with the lower concentration of cholesterol, while in the remaining system, the higher amount of cholesterol in the bilayer smears out the transitional behavior. Thus, we demonstrate the ability of the Slipids force field to predict the phase behavior of bilayers of SOPC and SOPC mixed with cholesterol. Full article

Cordyceps militaris, well known for its therapeutic potential in managing type-2 diabetes through the inhibition of α-amylase and α-glucosidase enzymes, was the central focus of this research, which investigated the influence of various cultivation substrates on its enzymatic inhibitory properties and bioactive compound content. Previous studies have primarily focused on the general pharmacological benefits of C. militaris but have not thoroughly explored how different substrates affect its bioactive profile and enzyme inhibitory activities. This study aimed to evaluate the impact of substrate selection on the enzyme inhibition activities and the levels of bioactive compounds such as cordycepin and adenosine in C. militaris, demonstrating that substrate selection markedly affects both these enzymes’ inhibition activities and bioactive compound levels. Particularly, C. militaris fruiting bodies grown on Brihaspa atrostigmella showed the highest concentrations of cordycepin (2.932 mg/g) and adenosine (1.062 mg/g). This substrate also exhibited the most potent α-glucosidase inhibition with an IC₅₀ value of 336.4 ± 16.0 µg/mL and the most effective α-amylase inhibition with an IC₅₀ value of 504.6 ± 4.2 µg/mL. Conversely, C. militaris cultivated on the solid residues of Gryllus bimaculatus displayed the strongest xanthine oxidase (XOD) inhibition, with the lowest IC₅₀ value of 415.7 ± 11.2 µg/mL. These findings highlight the critical role of substrate choice in enhancing the medicinal properties of C. militaris, suggesting that optimized cultivation can enhance the bioactive properties for more effective natural therapies for diabetes and other metabolic disorders. This study not only extends the understanding of C. militaris’ pharmacological potential but also illustrates its applicability in developing customized treatment options. Full article

Traditional separation membranes used for dye removal often suffer from a trade-off between separation efficiency and water permeability. Herein, we propose a facile approach to prepare cyclodextrin-based high-flux nanofiber membranes by electrospinning and vapor-driven crosslinking processes. The application of glutaraldehyde vapor for crosslinking hydroxypropyl-β-cyclodextrin (HP-β-CD)/polyvinyl alcohol (PVA)/laponite electrospun membranes can build interconnected structures and lead to the formation of a porous hierarchical layer. In addition, the incorporation of inorganic salt, laponite, can alter the crosslinking process, resulting in membranes with improved hydrophilicity and highly maintained electrospun nanofibrous morphology, which contributes to an ultrafast water flux of 1.0 × 10⁵ Lh⁻¹m⁻²bar⁻¹. Due to the synergetic effect of strong host–guest interaction and electrostatic interaction, the membranes exhibit suitable rejection toward anionic dyes with a high removal efficiency of >99% within a short time and achieve accurate separation for cationic against anionic dyes, accompanied by suitable recyclability with >97% separation efficiency after at least four separation–regenerations. The prepared membranes with remarkable separation efficiency and ultrafast permeation properties might be a promising candidate for high-performance membranes in water treatment. Full article