Aldehydes Research Articles

Vibrational and DFT Studies and Anticancer Activity of Novel Pd(II) and Pt(II) Complexes with Chloro Derivatives of 7-Azaindole-3-Carbaldehyde

This study investigates the structural, vibrational, and biological properties of novel palladium(II) and platinum(II) complexes with 5-chloro-7-azaindole-3-carbaldehyde (5ClL) and 4-chloro-7-azaindole-3-carbaldehyde (4ClL) ligands. Infrared and Raman spectroscopy, combined with DFT (ωB97X-D) calculations, provided valuable information about metal–ligand interactions, the cis or trans conformation of the aldehyde group in the ligands, and the presence of trans isomers in the metal complexes obtained in the solid state. In vitro tests were used to evaluate the antiproliferative activity of the novel complexes against several cancer cell lines, including ovarian cancer (A2780), cisplatin-resistant ovarian cancer (A2780cis), colon cancer (HT-29), and triple-negative breast cancer (MDA-MB-231), as well as normal mouse fibroblasts (BALB/3T3). The platinum complex, trans-[PtCl2(5ClL)2], exhibited superior activity against A2780cis (IC50 = 4.96 ± 0.49 µM) and MDA-MB-231 (IC50 = 4.83 ± 0.38 µM) compared to cisplatin, while the palladium complexes (trans-[PdCl2(4ClL)2] and trans-[PdCl2(5ClL)2]) demonstrated enhanced selectivity with reduced toxicity to normal fibroblasts (IC50 = 11.29 ± 6.65 µM and 14.98 ± 5.59 µM, respectively).

How the Electron-Transfer Cascade is Maintained in Chlorophyll-d Containing Photosystem I.

Photosystem I (PSI) from Acaryochloris marina utilizes chlorophyll d (Chld) with a formyl group as its primary pigment, which is more red-shifted than chlorophyll a (Chla) in PSI from Thermosynechococcus elongatus. Using the cryo-electron microscopy structure and solving the linear Poisson-Boltzmann equation, here we report the redox potential (Em) values in A. marina PSI. The Em(Chld) values at the paired chlorophyll site, [PAPB], are nearly identical to the corresponding Em(Chla) values in T. elongatus PSI, despite Chld having a 200 mV lower reduction power. The accessory chlorophyll site, A-1, in the B branch exhibits an extensive H-bond network with its ligand water molecule, contributing to Em(A-1B) being lower than Em(A-1A). The substitution of pheophytin a (Pheoa) with Chla at the electron acceptor site, A0, decreases Em(A0), resulting in an uphill electron transfer from A-1. The impact of the A-1 formyl group on Em(A0) is offset by the reorientation of the A0 ester group. It seems likely that Pheoa is necessary for A. marina PSI to maintain the overall electron-transfer cascade characteristic of PSI in its unique light environment.

Synthesis, Characterization and Biological Evaluation of N [3-Chloro-2 (aryl)-4-oxoazitidin-1-y] pyridine-4-carboxamide

Isoniazid on addition with different aromatic aldehyde gives Schiff’s bases. The Schiff base so formed on treatment with chloroacetyl chloride and triethyl amine as a base catalyst in 1-4 Dioxan gives product 2a-2n.The synthesized compounds characterized by spectral analysis like IR, NMR & Mass and elemental analysis. The compounds were screened by anticonvulsant and antimycobacterial activity.

Synthesis of 3-Substituted Indoles by Yonemitsu Three-Component Reactions Accelerated in Microdroplet/Thin Film.

3-Substituted indoles are an important framework of many drugs, agricultural chemicals, functional materials, and bioactive compounds. Malononitrile-based three-component Yonemitsu reactions are attractive choices for the synthesis of 3-substituted indole derivatives but suffered from long reaction time and harsh conditions (e.g., elevated temperature and special catalysts/solvents) in conventional conversions. In this study, we developed a metal-free, efficient, mild, and wide microdroplet/thin-film method to construct 18 3-substituted indoles from various substituted aromatic aldehydes and indoles with good reaction yields (42-69%) and fantastic reaction acceleration (1.32 × 103 rate acceleration factor relative to the bulk reaction). By spraying 0.8 mol L-1 reactants at 300 μL min-1, the rate of the microdroplet/thin film product was scaled up to 1.72 g h-1. Overall, the microdroplet/thin-film method offered several advantages including high efficiency, mild conditions, wide scope, and gram-scale ability, making it attractive for synthesizing 3-substituted indoles under the requirements of sustainable chemistry.

Synthesis and Biological Evaluation of some 2,5-Disubstituted -1,3,4- Oxadiazole Derivatives

Synthesis of some new 2, 5-diaryl-1, 3, 4-oxadiazole derivatives starting from Isoniazide (INH) is described. The target compounds 11- 20 were obtained by treating INH with various aromatic aldehydes and monosaccharides to give corresponding Schiff ’s bases 1- 10, which upon subsequent oxidation, by using either method A, B or C, yielded desired compounds. They were purified and characterized by spectroscopic techniques and elemental analyses. These compounds were evaluated for antibacterial, antifungal and antiviral activities. Compounds 11, 16 and 17 exhibited good antibacterial and antifungal activity, however, none of the compounds were enough active against various strains of virus.

Design and Synthesis of 1-(2-amino-1-(4-methoxyphenyl)ethyl) cyclohexanol Analogs as Potential Microbial Agents

1-(2-amino-1-(4-methoxyphenyl)ethyl)cyclohexanol (1), on condensation with chloroacetyl chloride yielded 2-chloro-N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)acetamide (2), which on amination with hydrazine hydrate yielded in turn 2-hydrazinyl-N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)acetamide (3). Compound 3, on condensation with various aromatic aldehydes afforded a series of 2-(2-benzylidenehydrazinyl)-N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)acetamides 4a-n, which upon dehydrative annulation in the presence of chloroacetyl chloride and triethylamine yielded 2-(3-chloro-2-oxo-4-phenylazetidin-1-ylamino)-N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl) acetamides 5a-n. The synthesized compounds 4a-g and 5a-g were screened for their antibacterial activity against four microorganisms: Staphylococcus aureus (Gram positive), Bacillus subtilis (Gram positive), Pseudomonas aeruginosa (Gram negative) and Escherichia coli (Gram negative). They were found to exhibit good to moderate antibacterial activity. The antifungal activities of these compounds were also tested against three different fungal species. None of them were active against the species tested.

Discovery of New Imidazolinones Derivatives as Potential Microbial Agents

A series of imidazolinone were prepared by heating the hippuric acid in presence of acetic anhydride and sodium acetate with different aromatic aldehydes gave 5-oxazolone derivatives which reacting with N-amino-2,3,4,5,6-pentafluoro benzamide in pyridine gave imidazolinone. All the synthesized compounds have been characterized on the basis of elemental analysis, IR, 1H-NMR and 13C-NMR spectral data. All the synthesized compounds have been screened against four different bacterial strains S. aureus, S. paratyphi-A, E. coli and B. subtilis and fungal strain F. molaniforme and A. niger. Some of the compound was endowed with a remarkable antibacterial as well as antifungal activity.

Green synthesis, anti-inflammatory evaluation and molecular docking of novel pyridines via one pot multi-component reaction using ultrasonic irradiation.

In this paper, we present a green application for the synthesis of novel pyridine derivatives 4a-f via one-pot, multicomponent reaction (MCRs) of some aromatic aldehydes 1a-f with malononitrile (2) and N-(4-acetylphenyl)-4-methylbenzenesulfonamide (3) in the presence of ammonium acetate using ultrasonic irradiation (U.S) in an aqueous solvent H2O:EtOH (2:1). The structures of all synthesized pyridines 4a-f were confirmed via elemental analysis and different spectroscopic techniques. This application has many advantages such as avoiding hazardous solvents, excellent yields, inexpensive, simple application, in addition to obtain pure compounds. The anti-inflammatory activity of the newly compounds was examined with the reference drug Ibuprofen. The obtained results showed that most derivatives are promising anti-inflammatory activates. Moreover, compound 4b exhibits the most anti-inflammatory activity with a percentage of inhibition with 51.67% compared with Ibuprofen 53.96%. Furthermore, the newly compounds were studied in their molecular docking simulations against the enzyme Human Cyclooxygenase-2, with Tolfenamic Acid as a reference ligand (PDB ID: 5IKT). Compound 4b demonstrated a robust binding affinity with the target protein 5ikt, evidenced by its binding affinity score of - 11.16 kcal/mol, which is the highest among the studied compounds.

Covalent Capture of Nanoparticle-Stabilized Oil Droplets via Acetal Chemistry Using a Hydrophilic Polymer Brush.

We report the capture of nanosized oil droplets using a hydrophilic aldehyde-functional polymer brush. The brush was obtained via aqueous ARGET ATRP of a cis-diol-functional methacrylic monomer from a planar silicon wafer. This precursor was then selectively oxidized using an aqueous solution of NaIO4 to introduce aldehyde groups. The oil droplets were prepared by using excess sterically stabilized diblock copolymer nanoparticles to prepare a relatively coarse squalane-in-water Pickering emulsion (mean droplet diameter = 20 μm). This precursor was then further processed via high-pressure microfluidization to produce ∼200 nm squalane droplets. We demonstrate that adsorption of these nanosized oil droplets involves acetal bond formation between the cis-diol groups located on the steric stabilizer chains and the aldehyde groups on the brush. This interaction occurs under relatively mild conditions and can be tuned by adjusting the solution pH. Hence this is a useful model system for understanding oil droplet interactions with soft surfaces.

Expeditious and environmentally benign synthesis of imidazo[4,5,1-ij]quinolines via sequential Povarov reaction/reductive cyclization.

In this contribution, a novel, simple, diastereoselective and environmentally benign two-step diversity-oriented synthesis of imidazo[4,5,1-ij]quinolines is described for the first time. The synthesis of the target compounds involves a deep eutectic solvent-mediated one-pot Povarov reaction leading to the obtention of 8-nitrotetrahydroquinolines, followed by a microwave-assisted reductive cyclocondensation employing different aromatic and aliphatic aldehydes. The target compounds were obtained in up to 70% overall yield starting from commercially available o-nitroanilines, natural phenylpropanoids (trans-anethole and trans-isoeugenol) and aromatic or aliphatic aldehydes. The eutectic solvent employed in the first step was reused in four runs without observing a drastic decrease in catalytic activity, and sodium dithionite showed to be an efficient and green reducing agent for the second step. This methodology provides significant advantages in terms of synthetic and green chemistry such as mild reaction conditions, short reaction time, energy-efficiency, simple work-up procedure, low cost, scalability and utilization of renewable substrates and a reusable solvent.

Decatungstate-Photocatalyzed Transformations of 2-Bromo-3,3,3-trifluoropropene for Selective Synthesis of Z/E-β-CF3-Enones.

Condition-controlled switchable and divergent transformations of cost-effective 2-bromo-3,3,3-trifluoropropene (BTP) and aldehydes were realized using a decatungstate (TBADT)-photocatalyzed strategy. The hydroacylated products, i.e., β,β-Br,CF3-ketones, can be applied as highly functionalized synthetic building blocks for the selective synthesis of (Z/E)-β-CF3-enones. Utilizing this methodology, a broad range of commercially available aromatic and aliphatic aldehydes as well as numerous complex aldehydes, such as lily aldehyde, cyclamen aldehyde, citronellal, vanillin, and aldehydes containing bioactive moieties, including ibuprofen, gemfibrozil, naproxen, flurbiprofen, oleic acid, and aspirin, may be proficiently employed in this transformative process.

Pd anchored to layered double hydroxide modified with chitosan and Echinophora platyloba extract as a nanocatalyst for the formylation of aryl iodides with formic acid.

The novel Zn-Cu-Al layered double hydroxide (LDH) encapsulated within a chitosan/glutaraldehyde matrix, designated as LDH@Cs/G@Pd, was synthesized through simplified methodologies for the preparation of aromatic aldehyde derivatives. Formic acid served as the carbon monoxide source and hydrogen donor, while chitosan/glutaraldehyde acted as the linking agent between the substrate and palladium nanoparticles, with Echinophora platyloba extract functioning as the reducing agent for palladium. The characterization of LDH@Cs/G@Pd was conducted using a variety of analytical techniques, including Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDS), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area analysis, and inductively coupled plasma optical emission spectroscopy (ICP-OES). The results indicate that the catalyst has been successfully synthesized and Showed promising characteristics for its intended application. Afterward, the catalyst was utilized to Synthesize aromatic aldehydes. The catalyst developed in this study demonstrated a synthesis yield of approximately 95 % for aromatic aldehydes, confirming its potential as an effective candidate for industrial applications.

Highly Efficient and One-pot New Betti Bases: PEG-400 and Al2O3 Mediated Synthesis, Optimizations, and Cytotoxic Studies

Background: Multicomponent reactions (MCRs) have proven as one of the best alternatives to minimize several environmental consequences, mainly the use of hazardous chemicals, byproducts, and severe production processes. Literature reveals that MCRs with PEG-400 and metal oxide-based greener media provide a new and useful strategy for the construction of biologically potent organic systems. Objective: The present study aimed to synthesize newer Betti bases by a modified Betti reaction employing a highly efficient catalyst for the direct synthesis of a novel class of non-racemic amino benzyl naphthol ligands under green solvent media. The involvement of the articulated framework (4a-4j) was studied against nine cancer panels (NCI-60 cell lines) in terms of inhibiting/killing cancer cells. Methods: For the modification of the Betti reaction, we used 2-aminopyridin-3-ol, aromatic aldehydes, and a naphthol system using greener media employing PEG-400 and alumina as a prime active and highly selective catalyst. Furthermore, the antiproliferative activity against NCI-60 human cancer cell lines (GI50) was used for the development of pharmacologically active compounds and exhibited the single dose (10-5 M) study. Results: Based on greener media synthesis, recompenses of ease of workup, less reaction time, higher yield, and higher atom economy, as well as environmentally friendly, were reported. Betti bases were obtained at a yield of 87-98% and characterized by spectroscopic techniques. Among the synthesized scaffolds, compound 4b was found to be extra potent in melanoma cancer [MDAMB- 435], while compound 4h showed promising inhibition in leukemic cancer cell lines [HL- 60(TB) and MOLT-4]. Conclusion: A straightforward way for an efficient synthesis of Betti bases was developed via the reaction of naphthol and aldehydes with amines in PEG-400 media. An Al2O3 was effectively catalyzed in the Betti reaction in excellent yields without the formation of any other by-product in atom economy and environmentally benign way. The newly synthesized hybrids were tested in vitro against a panel of cancer cell lines, and some of the compounds exhibited significant inhibitory anti-proliferative effects. The most potent compounds (4b and 4h) showed interesting results, and compound 4b was found extra potent in melanoma cancer cell lines with -62% GI values.

An investigation of the potential of rhodamine B hydrazide as a fluorescent probe for enhancing latent fingerprints

A series of novel rhodamine B hydrazide derivatives were synthesized by refluxing rhodamine B hydrazide with various aromatic aldehydes, including 3-nitrobenzaldehyde, 4-nitrobenzaldehyde, 4-chlorobenzaldehyde, 4-hydroxybenzaldehyde, cinnamaldehyde, piperonal, and veratraldehyde. The resulting hydrazones were purified and characterized through techniques including melting point determination, UV–Vis spectroscopy (λmax ranging from 245 to 555 nm), infrared (IR) spectroscopy, and proton nuclear magnetic resonance (NMR) spectroscopy. The derivatives exhibited strong fluorescence with enhancements up to 90 % at optimized wavelengths, facilitating their use in latent fingerprint visualization. Yields of the purified derivatives exceeded 85 %, with melting points in the range of 172–188 °C. Notably, certain derivatives enhanced latent fingerprint contrast by up to 60 % on glass surfaces, indicating significant potential in forensic applications. This study demonstrates a cost-effective and environmentally friendly synthesis method that provides high yields of pure fluorescent agents suitable for forensic science.

1,3-Naphthoxazine derivatives: Synthesis, in silico pharmacokinetic studies, antioxidant and photoprotective properties

Investigation into the interactions between photoprotective agents and skin can offer a precise understanding of their biological behaviors in vitro and in vivo, providing crucial insights for generating new substances. For this purpose, we designed and synthesized a series of naphthoxazine derivatives and examined their photoprotective properties. 1,3-naphthoxazine derivatives were synthesized through the multi-component reaction of 2-naphthol, arylamines and aromatic aldehydes in the presence of copper(II) trifluoromethanesulfonate (Cu(OTf)2) and (±)-Camphor-10-sulfonic acid ((±)-CSA) catalyst system under sonication. The potential of these synthesized 1,3-naphthoxazine derivatives as antioxidants and viable organic structural-based sunscreen ingredients has been investigated. Sun protection factor (SPF) assay results showed that especially compounds 4i, 4c, 4k, 4d, 4r, and 4h had remarkably high activity (23.65, 23.57, 23.04, 21.94, 20.80, and 20.26, respectively at 900 µg/mL concentration). Additionally, antioxidant activity of the synthesized compounds was evaluated and compounds 4h, 4e, 4b, and 4j exhibited the highest activities in DPPH scavenging activity assay (86.46 %, 82.83 %, 80.78 %, and 80.65 % respectively at 400 µg/mL concentration). The synthesized compounds exhibit promising characteristics for effective UV radiation absorption, suggesting their suitability for inclusion in sunscreen formulations. Cytotoxic activity of compound 4k against normal human fibroblast cell line (MRC-5) was determined by CVDK-8 method. The results revealed that the compound provided remarkable viability (87.55 %) of MRC-5 cells at concentration of 100 µM. The study explores their efficacy in providing broad-spectrum protection against UVA and UVB rays, degradation and photostability, ADMET profile, and other pharmacokinetic properties.

Synthesis and investigation of photo-physical properties of fluorescent dyes obtained by the Knoevenagel condensation of mono-, di- or tri-formyl aromatic aldehydes and various CH-acid derivatives

Fluorescent dyes were constructed using the Knoevenagel condensation of the appropriate aldehydes and CH-acid derivatives. Aromatic aldehydes containing one, two or three formyl groups were used as substrates. Cyanoacetamide, ethyl cyanoacetate, benzoylacetonitrile and indan-1,3-dione play the role of CH-acid derivative. The appropriate aldehydes were obtained by the Duff formylation reaction. The dyes synthesis procedure was very simple. The condensation was carried out in water in the presence of NaOH, as the basic catalyst at room temperature, and the dyes were obtained in yields between 58-93%. The work-up procedure was very simple, and the products do not require any further purification. The great advantages of this synthetic procedure are its simplicity, cheapness, compliance with the rules of green chemistry and the fact that it efficiently leads to structurally complex fluorescent dyes. Twenty-three new compounds were obtained, eleven of which exhibited fluorescence in solution and four in the solid state. Taking into account the fluorescence quantum yield and the emission maximum value close to the NIR range, the dye constructed by condensation of indan-1,3-dione and methyl 3,5-diformyl-4-hydroxybenzoate meets the above-mentioned requirements (Φ=16%, λem= 660 nm) best. The dye with the highest value of Φ = 25% in solid is a derivative of cyanoacetamide and 3,4,5-trimethoxybenzaldehyde.

Insight into the reaction route and the effect of Brønsted and Lewis acid for alkylation of 5-Hydroxymethylfurfural

5-Hydroxymethylfurfural (HMF) can be upgraded to ether as fuel or fuel additives through conversion of the hydroxyl and aldehyde groups. The two groups are always involved in different catalytic reactions, such as etherification, acetalization, hydrogen transfer reduction, and even ring-opening reactions. This makes the etherification upgrading of HMF with high selectivity to desired product a great challenge. In the present wok, transformation of HMF in isopropanol was systematically investigated over different catalysts with Brønsted acid and Lewis acid sites. The effect of catalytic sites on product distribution and selectivity was studied. Moreover, several products, such as 5-isopropoxymethylfurfural, 5-isopropoxymethylfurfuryl alcohol, 5-isopropoxymethylfurfuryl alcohol, and 2,5-furandimethanol, were obtained with high selectivity, and the conversion pathway of HMF with alcohols on different catalytic sites was revealed under different catalytic conditions. The transformation of HMF to furan triether products over multi-site catalyst was realized for the first time based on the proposed reaction pathway with excellent activity and selectivity.

Computational Studies and Antimicrobial Activity of 1-(benzo[d]oxazol-2- yl)-3,5-diphenylformazan Derivatives.

Due to the biological importance of the benzoxazole derivatives, some 1- (benzo[d]oxazol-2-yl)-3,5-diphenyl-formazans 4a-f were synthesized and screened for in-silico studies and in-vitro antibacterial activity. The benzo[d]oxazole-2-thiol (1) was prepared by reacting with 2-aminophenol and carbon disulfide in the presence of alcoholic potassium hydroxide. Then 2-hydrazinylbenzo[d] oxazole (2) was synthesized from the reaction of compound 1 with hydrazine hydrate in the presence of alcohol. Compound 2 was reacted with aromatic aldehydes to give Schiff base, 2-(2- benzylidene-hydrazinyl)benzo[d]oxazole derivatives 3a-f. The title compounds, formazan derivatives 4a-f, were prepared by a reaction of benzene diazonium chloride. All compounds were confirmed by their physical data, FTIR, 1H-NMR, and 13CNMR spectral data. All the prepared title compounds were screened for in-silico studies and in-vitro antibacterial activity on various microbial strains. Molecular docking against the 4URO receptor demonstrated that molecule 4c showed a maximum dock score of (-) 8.0 kcal/mol. MD simulation data reflected the stable ligand-receptor interaction. As per MM/PBSA analysis, the maximum free binding energy of (-) 58.831 kJ/mol was exhibited by 4c. DFT calculation data confirmed that most of the molecules were soft molecules with electrophilic nature. The synthesized molecules were validated using molecular docking, MD simulation, MMPBSA analysis, and DFT calculation. Among all the molecules, 4c showed maximum activity. The activity profile of the synthesized molecules against tested micro-organisms was found to be 4c>4b>4a>4e>4f>4d.

Hydrophobic and decay-resistant green building wood modified by aromatic aldehydes based on Schiff base

Hydrophobic and decay-resistant green building wood modified by aromatic aldehydes based on Schiff base

Combinatorial Synthesis of Indole Derivatives as Anti-oomycetes Agents.

Developing high-efficiency and low-risk small-molecule green fungicide is the key to effective control of the plant pathogenic oomycetes. Indole is an important raw material for drug synthesis. Due to its unique structural skeleton, indole, and its derivatives have exhibited a wide range of biological activities. However, a study on the synthesis of novel indole derivatives as fungicidal agents against Phytophthora capsici has not yet been reported. The important intermediates 2a-c and 3a-c were synthesized in high yields by Vilsmeier- Haack and Knoevenagel reactions with indole as the lead compound. Furthermore, different substituted benzenesulfonyl groups were introduced into the NH position of the indole ring, and twelve indole derivatives (I-a-l) were prepared. Their structures were well characterized by 1H NMR, HRMS, and melting point. The results showed that 2-[(N-(4-nitrobenzenesulfonyl)-indole-3)-methylene]-diethyl malonate (I-d) and 2-[(N-(4-nitrobenzenesulfonyl)-5-cyanoindole-3)-methylene]-diethyl malonate (I-l) showed more anti-oomycete activity against P. capsici than the commercialized fungicide zoxamide, with corresponding EC50 values of 26.53, 23.48 and 28.16 mg/L, respectively, and the protective effect of the compounds against P. capsici in vivo further confirmed the above results. The preliminary structure-activity relationship showed that the formyl group modification at the C-3 position of the indole ring was acceptable, and the different anti-oomycete activities of R1 and R2 were significantly different, with R1 being 5-CN > H > 6-Me, and R2 being 4-NO2 > 3-NO2, H > 4-Me.