Schiff Base Research Articles

Room-temperature synthesis of covalent organic frameworks with dual functional groups for high-performance adsorption of diclofenac sodium from aqueous solution

Diclofenac sodium (DCF) are commonly found in ambient waterways due to its widespread use, and this poses significant risks to both human health and ecosystems. In this study, we have designed and synthesized a series of imine-linked covalent organic frameworks (COFs) with dual functional groups using a triple assembly strategy. Specifically, the platform molecules 2,5-dimethoxyterephthalaldehyde (DMTP), 2,5-dihydroxyterephthalaldehyde (DHTP), and 1,3,5-tris(4-aminophenyl)benzene (TAPB) were employed for the direct fabrication of COFs through Schiff base condensation reactions. As a proof of concept, three room-temperature synthesized COFs (COF TAPB-DMTP-[OH]n, where n represents the molar mass of DHTP, with n values of 0.02, 0.03, and 0.04) were used for DCF adsorption from water. The adsorption isotherms, kinetics, pH effects, ionic strength, co-existing ions, and COF regeneration for DCF were thoroughly investigated. The incorporation of methoxy (-OMe) and hydroxyl (-OH) groups serves as a functional strategy to facilitate hydrogen bonding interactions with DCF molecules. Consequently, the developed COFs, featuring an ultrahigh surface area and mesoporous structure, demonstrated a maximum adsorption capacity of 413.2mg/g and a rate constant k2 of 0.0435g/mg/min, which exceeds the performance of the majority of previously described adsorbents. The adsorption capacity toward DCF remained nearly unchanged after five regeneration cycles of the COF. Furthermore, the self-prepared adsorbent demonstrated efficient adsorption of DCF from real environmental water, indicating its potential for practical DCF removal applications.

Synthesis, in vitro and in silico study of novel 1,3-diphenylurea derived Schiff bases as competitive α-glucosidase inhibitors.

Diabetes mellitus has become a major global health burden because of several related consequences, including heart disease, retinopathy, cataracts, metabolic syndrome, collapsed renal function, and blindness. In the recent study, thirty Schiff base derivatives of 1,3-diphenylurea were synthesized and their anti-diabetic activity was evaluated by targeting α-glucosidase. The compounds exhibited an overwhelming inhibitory potential for α-glucosidase with higher potency ranging from 2.49-37.16 μM. The most effective compound, 5h, showed competitive inhibition of α-glucosidase (K i = 3.96 ± 0.0048 μM) in the kinetic analysis and strong binding interactions with key residues α-glucosidase in docking analysis, indicating its potential for better glycemic control in diabetes patients.

A Schiff base hydrogel of oxidized okra gum and carboxymethylated chitosan: a biocompatible and biodegradable injectable system for drug delivery in wound care

A Schiff base hydrogel of oxidized okra gum and carboxymethylated chitosan: a biocompatible and biodegradable injectable system for drug delivery in wound care

Pyrazolone-Based Zn(II) Complexes Display Antitumor Effects in Mutant p53-Carrying Cancer Cells.

The synthesis and characterization of nine Schiff bases of pyrazolone ligands HLn (n = 1-9) and the corresponding zinc(II) complexes 1-9 of composition [Zn(Ln)2] (n = 1-9) are reported. The molecular structures of complexes 2, 3, 4, 8, and 9 were determined by single-crystal X-ray diffraction analysis, highlighting in all cases a distorted tetrahedral geometry around the Zn(II) ion. Density functional theory studies are performed on both the HLn ligands and the derived complexes. A mechanism of dissociation and hydrolyzation of the coordinated Schiff base ligands is suggested, confirmed experimentally by powder X-ray diffraction study and photophysical studies. Complexes 1-9 were investigated in vitro as anticancer agents, along with mutant p53 (mutp53) protein levels in human cancer cell lines carrying R175H and R273H mutp53 proteins. Only those complexes with the highest Zn(II) ion release via dissociation have shown a significant cytotoxic activity with reduction of mutp53 protein levels.

All-natural hydrogel composed of carboxymethyl chitosan and oxidized dextran for promoting wound healing by immune-microenvironment regulation

Chronic wound treatment has always been a major clinical challenge owing to complex and dynamic wound microenvironment. The design and development of effective management with antimicrobial activity, ROS-scavenging and regulation immune response is vital for tissue repair. Herein, we developed puerarin (PUE) loaded a double network hydrogel consisting of methacrylated carboxymethyl chitosan and oxidized dextran with Schiff base and photo-crosslinking reaction. The composite hydrogel presented fast self-healing and outstanding compressive performance to bear deformation. The hydrogel exhibits a cumulative drug release pattern with biphasic release, which offers great potential for accelerating tissue healing at all stages of wounding. In addition, the hydrogel has good biocompatibility, antimicrobial ability and tube-forming ability in vitro. The full-thickness skin wound model of Staphylococcus aureus infection showed that the hydrogel dressing can accelerate tissue repair. This study demonstrated that the design of combing natural biomacromolecules with traditional Chinese medicine could be severed as a promising candidate biomaterial for skin tissue recovery.

Designing of some VO(II), Co(II) and Hg(II) Schiff base complexes: Synthesis, structure elucidation, anticancer and biopesticidal activities, DFT and docking approaches

New VO(II), Co(II) and Hg(II) chelates of bi- or tetradentate isatin based ligand i.e.:-2-(((E)-2-oxo-1,4-dihydrocyclohepta [b]pyrrol-3(2H)-ylidene)amino)-N-(8-((1-(2-((E)-2-oxoindolin-3-phenyl)vinyl) amino) naphthalen-1-yl) benzamide (H2L) were synthesized and well characterized. The reaction between N,N′-(naphthalene-1,8-diyl)bis(2-aminobenzamide) and di-oxazine-2,4 dione (isatin) yielded the Schiff base (H2L). The compounds have been identified by different physicochemical and spectroscopic approaches and DFT as well. From all measurements square pyramidal, distorted octahedral or square planar configurations have been suggested for the chelates 1, 2 and 3, respectively. The Coats-Redfern equations were used to calculate and define the dynamics properties of decomposition stages from TGA (Ea, A, ΔH*, ΔS*, and ΔG*). The in vitro anticancer property of the obtained compounds towards human hepato (HepG2) and human breast (MCF-7) carcinoma cell lines has been screened. Also, the biopesticidal effect of these compounds against spodoptera littoralis has been examined. Data showed that, the tested [Hg(H2L)(L)] complex (3) possesses the most anticancer efficacy against both HepG2 and MCF-7 cells, with half inhibitory concentration (IC50) = 5.78 ± 0.029, 11.24 ± 0.58 μg/mL, respectively also, this complex considered as good an insecticide with the concentration lethal to 50 percent of test organisms (LC50) = 27585.45 ppm after 72 h. The insecticide and tumor inhibition properties were compared with the theoretical molecular docking findings with the specification of the active species in the designated proteins.

An Integrated All-Natural Conductive Supramolecular Hydrogel Wearable Biosensor with Enhanced Biocompatibility and Antibacterial Properties.

Conductive hydrogels exhibit tremendous potential for wearable bioelectronics, biosensing, and health monitoring applications, yet concurrently enhancing their biocompatibility and antimicrobial properties remains a long-standing challenge. Herein, we report an all-natural conductive supramolecular hydrogel (GT5-DACD2-B) prepared via the Schiff base reaction between the biofriendly dialdehyde cyclodextrin and gelatin. The potent antibacterial agent fusidic acid (FA) is incorporated through host-guest inclusion, enabling 100% inhibition of Staphylococcus aureus proliferation. The biocompatibility of our hydrogel is bolstered with tannic acid (TA) facilitating antibacterial effects through interactions with gelatin, while borax augments conductivity. This supramolecular hydrogel not only exhibits stable conductivity and rapid response characteristics but also functions as a flexible sensor for monitoring human movement, facial expressions, and speech recognition. Innovatively integrating biocompatibility, antimicrobial activity, and conductivity into a single system, our work pioneers a paradigm for developing multifunctional biosensors with integrated antibacterial functionalities, paving the way for advanced wearable bioelectronics with enhanced safety and multifunctionality.

Ni(II)/Yb(III)-metallogels for distinctive fluorescent ‘turn-on’ detection of m-phenylenediamine: Toward construction of multiple logic gates

New versatile Schiff base gelator (HL) and its highly selective Ni(II)-and Yb(III)-based metallogels 1–2 have been synthesized and characterized by spectral techniques. Gelator HL in presence of triethylamine (Et3N) with Ni(NO3)2·6H2O and anhydrous Yb(NO3)3 in DMF/MeOH(1:1) solvents forms MG1 and MG2 supramolecular gels, respectively at room temperature (rt). Rheological results show thermal stability up to 100 ℃ and structurally rigid nature of MG1 and MG2. Remarkably, MG1 and MG2 were examined for identification of cations, anions, nitroaromatics and aromatic amines (AAs) but unable to recognize any analytes except for m-phenylenediamine (MPD) by using MG1. Metallogel MG1 shows highly selective response to MPD environmental pollutant with a limit of detection (LoD) of 7.58 × 10-7 M, without any interference of competing analytes. Interestingly, depending upon fascinating fluorescent On-Off-On switching behavior, molecular logic device has been fabricated with AND and IMPLICATION-logic gates function by employing the chemical inputs (i) HB, Ni(II) (MG1), Yb(III) (MG2) and (ii) HB, MG1 and MPD based on emission change at different wavelengths as output signal.

The synthesis of Fe3O4@SiO2-NNO-CuII nanocatalyst and investigation of its application in the synthesis of imidazo[1,2-a]pyridines

In this study, a tridentate Schiff base ligand obtained from the condensation of salicylaldehyde and 3-amino-1,2,4 triazole was covalently immobilized on the surface of 3-chloro-trimethoxysilane-functionalized magnetic nanoparticles. This nitrogen and oxygen-rich compound provides donor arms for the coordination of copper ions. The prepared nanocatalyst (Fe3O4@SiO2-NNO-CuII) has been characterized by various techniques including FT-IR, EDX, SEM, VSM, XRD and ICP analysis and used as an efficient recyclable catalyst for the synthesis of imidazo[1,2-a]pydidines. Imidazo[1,2-a]pyridine products were obtained through the coupling reaction of substituted benzaldehydes, 2-aminopyridine derivatives and phenylacetylene under solvent-free conditions in high yields and short reaction times.

Carboxymethyl chitosan-dialdehyde glucan/polydopamine carrier targeted delivery Bacillus subtilis on enhancing oral utilization and intestinal colonization in mice

Most probiotics are difficult to resist the invasion of gastrointestinal physiological and pathological environments, which limits their beneficial effects. The design of a pH-responsive and adhesive double-layer carrier (Carboxymethyl chitosan polyaldehyde polysaccharide, CMCS-DHG/PDA) aims to safeguard the activity of probiotics and enhance their intestinal colonization. The results obtained from UV–vis spectroscopy and XPS analysis revealed the formation of a polydopamine nanocoating surrounding Bacillus subtilis, and the outer carrier formed a Schiff base covalent bond, providing sufficient mechanical properties for the carrier. The carrier exhibited a significantly higher degree of swelling under pH 1.2 compared to pH 7.4, indicating its pronounced pH responsiveness. The CMCS-DHG/PDA carrier not only provided protection for B. subtilis against simulated digestive fluids, but also improved its tolerance to bile and antibiotics. In addition, carrier-protected probiotics showed extraordinary mucosal adhesion, which could significantly improve oral bioavailability and intestinal colonization. Finally, the impact of carrier-protected B. subtilis on gut microbiota was explored, revealing that the carrier protected B. subtilis could significantly improve the diversity, richness, and composition of gut microbiota. Concurrently, it promoted the formation of short chain fatty acids, creating a more beneficial environment for intestinal health.

Construction of chitosan/carboxylated polyvinyl alcohol/poly(N-isopropylacrylamide) composite antibacterial hydrogel for rapid wound healing

In the realm of skin injury management, the expedited closure of wounds, prevention of scar formation, and enhancement of the healing process are of critical significance. The creation of economical dressings that effectively facilitate swift wound sealing in the initial phase of skin trauma while curbing scar development represents a promising avenue for clinical utility. Within the context of this investigation, we synthesized a novel hydrogel composed of chitosan (CS), carboxylated poly(vinyl alcohol) (PVA-COOH) via a Schiff base reaction between carboxylated PVA and chitosan, yielding networks abundant in amide bonds. Following this, a chitosan/carboxylated PVA/poly(N-isopropylacrylamide) hydrogel (CNP) was engineered by incorporating poly-N-isopropylacrylamide chains for interpenetration at ambient temperature. Our findings indicate that the CNP hydrogel exhibits favorable degradability and swelling characteristics. Moreover, it possesses favorable antimicrobial efficacy and biocompatibility. In a murine full-thickness skin injury model, the hydrogel was found to expedite wound healing by augmenting granulation tissue formation, mitigating wound inflammation, and promoting angiogenesis.

Synthesis, crystal structure, biological and docking studies of 5-hydroxy-2-{[(2-methylpropyl)iminio]methyl}phenolate.

Background: Schiff base compounds are potential drugs.Results: A Schiff base compound prepared by condensing 2,4-dihydroxy benzaldehyde and isobutylamine was characterized for structure, thermal, physicochemical and biological properties. The keto-enol tautomerism and azomethine functionality enhances electron delocaliZation and biological activity. The compound showed good antibacterial and antifungal activity at 40μg/ml against bacteria such as Escherichia coli and Staphylococcus aureus and fungi like Candida albicans and Candida tropicalis. The docking study exhibits a moderate binding affinity for the GyrB protein in E. coli with a binding energy of -4.26kcal/mol.Conclusion: The compound exhibits enhanced biological activity and suppression of cell growth at concentrations as low as 30μg/ml. The IC50 for MFC-7 was found to be 41.5μg/ml.

Intramolecular hydrogen bonding steered optical recognition of fluoride ion and consequent opto-chemical logic responses: Spectroscopic and computational studies

This work demonstrates the synthesis and characterization of a thiosemicarbazide core containing Schiff base molecule (MNHC) and its use as a chemosensor for the selective, ratiometric, and colorimetric detection of fluoride ions. The study reveals that in the presence of F− ions, MNHC displays a ratiometric change of absorption maxima at two different wavelengths (432 and 330 nm). MNHC involves an intramolecular hydrogen bonding initiating the possibility of keto-enol tautomerism which is thoroughly investigated by DFT study. Interestingly, the intramolecular hydrogen bonding enhances the acidity of the –NH proton and consequently the –NH center becomes more labile for F− ions binding over the other –NH proton. This fact is confirmed by 1H NMR study. Remarkably, F− ion forms intermolecular hydrogen bonding with the –NH moiety disrupting the intramolecular hydrogen bonding. The changes in absorption spectra in the presence of F− ions occur due to the intermolecular hydrogen bonding-assisted abstraction of the –NH proton. On the other hand, when H2O is added to the MNHC-F− composite, the spectroscopic signature of free MNHC is completely regenerated due to the transfer of proton from H2O to the nitrogen center of MNHC. In addition, 1:1 binding stoichiometry and 53.7 μM detection limit for fluoride ion are also confirmed. Moreover, utilizing these spectroscopic responses, different kinds of important opto-chemical logic gates like YES, NOT, PASS 0, PASS 1, INHIBIT, TRANSFER, and IMPLICATION are developed. Moreover, the F− ion-assisted competitive nature between the intramolecular vs intermolecular hydrogen bonding is thoroughly explored by substantial DFT study.

Injectable Silver Nanoparticle-Based Hydrogel Dressings with Rapid Shape Adaptability and Antimicrobial Activity.

Burns and scalds often result in deep wounds that challenge adequate debridement and inflammation control using traditional sheet-like hydrogel dressings. Herein, we developed an antibacterial, injectable, and self-healing hydrogel (ADCM@Ag) by employing carboxymethyl chitosan (CMCS) for in situ green reduction of silver ions and utilizing a spontaneous Schiff base reaction with aldehyde-functionalized dextran (AD). SEM analysis revealed a porous structure within the hydrogel. Swelling and enzymatic degradation assays demonstrated that ADCM@Ag hydrogel possesses excellent fluid absorption capacity and biodegradability. Mechanical tests indicated good mechanical properties, allowing the hydrogel to withstand external forces when applied to animal wounds. The hydrogel exhibited good injectability, shape adaptability, and self-healing capability. Cell experiments showed that the ADCM@Ag hydrogel avoided the cytotoxicity caused by high concentrations of silver ions and had good cell compatibility. Antimicrobial assays showed that ADCM@Ag exhibited potent bactericidal effects against Gram-negative and Gram-positive bacteria, achieving at least 85% killing efficacy. Collectively, ADCM@Ag hydrogel has good potential for wound dressing applications.

Constructing covalent organic frameworks with dense thiophene S sites for effective iodine capture

Developing versatile sorption materials for radionuclide capture (e.g. iodine) is critical for nuclear energy and environmental science. Covalent organic frameworks (COFs) have recently become a new platform for developing sorption materials because of their high surface area and functionalised skeleton structure. Herein, two types of COF materials containing thiophene were designed as iodine sorbents and synthesised via a Schiff base reaction of benzo[1,2-b:3,4-b’:5,6-b’’]trithiophene-2,5,8-tricarbaldehyde, benzidine (DADP) and p-phenylenediamine (DAB): DADP-COF and DAB-COF. DAB-COF exhibits a unique granular-rod-like morphology and has a higher surface area (1775 m2/g) than DADP-COF (1140 m2/g), which is clearly beneficial for the physical adsorption of iodine. Meanwhile, the COF backbone is rich in N and S sites, which are advantageous for the chemical adsorption of iodine. These two features make the two prepared COFs ideal iodine sorption materials. DAB-COF demonstrates an excellent gaseous iodine adsorption capacity of 4.2 g/g, ranking it as one of the most effective iodine sorption materials, while DADP-COF exhibits a good adsorption capacity of over 235 mg/g for iodine in cyclohexane solutions. Density functional theory calculations prove that imine N and thiophene S serve as active sites during the iodine adsorption. DAB-COF exposes more active sites because of its higher surface area, leading to a higher iodine adsorption capacity than DADP-COF. The results of this study indicate that introducing thiophene to COFs improves sorption efficacy for sorption applications in general and particularly paves the way for developing stable and effective COF sorbents for iodine capture from various environments.

Vanillin-crosslinked gelatin-polyvinyl alcohol aerogels: Improved physicochemical properties and antimicrobial activity

Crosslinking is a promising way to fabricate high-performance aerogels. In this study, vanillin (Van) crosslinked gelatin–polyvinyl alcohol (Gel−PVA) aerogels were prepared by vacuum freeze-drying method. The effects of different addition levels of Van on FTIR spectra, microstructures and physicochemical properties including water stability, mechanical properties, thermal stability and thermal insulation properties of aerogels were characterized, and antimicrobial activity of aerogels were validated. The results showed that Van exerted its crosslinking function through Schiff base bonding with Gel and hydrogen bonding with Gel and PVA. Although Van addition caused a slight decline in the thermal insulation performance and the obvious increase in pore diameter of aerogels, moderate Van crosslinking contributed to water stability, mechanical properties and thermal stability of aerogels. Besides, Van crosslinked Gel−PVA aerogel could effectively inhibit the growth of E. coli and B. cinerea. This suggests that the aerogel has promising applications in antimicrobial food packaging.

Constructing ESIPT-Capable α-Cyanostilbene Luminogens: Influence of Different Aromatic Substitutions Tethered to H-Acceptor (CH = N) on Photophysical Properties, Cu2+ and Fe3+ Detection.

Herein, two excited-state intramolecular proton transfer (ESIPT)-capable α-cyanostilbene luminogens were synthesized by Schiff base reaction of salicylaldehyde-like α-cyanostilbene candidate with 1-naphthylamine and 3-biphenylamine, respectively. We systematically analyzed their photophysical properties compared with their analogue, and demonstrated that their fluorescence behaviors could be elaborately modulated by different aromatic substitutions tethered to H-acceptor (CH = N). In virtue of the outstanding solid fluorescence, the 3-biphenylamine-decorated fluorophore was applied for monitoring Cu2+/Fe3+ qualitatively on the TLC-based test strip in real time and sensing Cu2+/Fe3+ quantitatively in the THF/H2O medium (fw = 90%, pH = 7.4). When the probe chelated with Cu2+/Fe3+, similar "turn-off" fluorescence signal outputs were triggered. From the fluorescence titration experiments, the detection limits were evaluated as 7.97 × 10- 8 M for Cu2+ and 8.24 × 10- 8 M for Fe3+, and the binding constant (Kα) values of the complexes were found to be 7.80 × 104 M-1 for Cu2+ and 9.06 × 104 M-1 for Fe3+. Job's plots indicated that probe complexed with Cu2+/Fe3+ in a 2:1 binding stoichiometry ratio. Furthermore, the probe was used to accurately quantify the Fe3+ spiked in real water specimens. This study offered a new perspective to construct ESIPT-capable α-cyanostilbene luminogen as the potential luminescent probe.

Biological study with molecular mechanism of imidazothiazole based Schiff bases as anti-Alzheimer agent: Insight into the role of synthesis, molecular docking and ADMET analysis

The current study aims to develop synthetic route and biological evaluation regarding a series of fused imidazothiazole derived Schiff base hybrid derivatives (1–17), synthesized by treating imidazothiazole bearing ester with hydrazine. The first intermediate imidazothiazole bearing hydrazide upon treating with ammonium thiocyanate was cyclized in the presence of 1,2-dioxane and potassium carbonate to second intermediate fused imidazothiazole bearing 2-aminothiadiazole. This intermediate was then mixed substituted benzaldehyde to afford fused imidazothiazole derived Schiff base hybrid derivatives. The current study revealed that the synthesized derivatives were examined and found with high inhibition profile against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in-comparison with marketed drug donepezil (IC50=7.20 ± 0.10 and 7.80 ± 0.20 µM for AChE and BuChE). Among all the derivatives, analog 11 (IC50=2.10 ± 0.30 and 2.80 ± 0.20 µM) was the one having highest inhibitory profile against both enzymes due to attachment of highly active tri-fluoromethyl group and hence regarded as potent analog. Furthermore, analog 7, 8, 9, 12 and 14 were also studied to exhibit excellent activity due to the attachment of electron donating groups and were found modest in contrast with the standard marketed drug. Protein-ligand interactions were observed through in-silico docking studies and their drug likeness properties were studied through ADMET analysis.

Novel tryptamine decorated cyclotriphosphazene derived Schiff base compounds: Synthesis, characterization and molecular docking studies

In this study, new cyclotriphosphazene derivative Schiff base compounds including tryptamine units were synthesized for the first time. The structures of all compounds (2–9) were characterized by FT-IR, mass, 1H and 31P NMR spectra. In addition, the solid-state structure and geometry of salicylaldehyde-substituted cyclotriphosphazene compound 6 using as the precursor were determined by single-crystal X-ray analysis. Molecular docking studies were performed to elucidate the interactions between target molecules and the compounds under investigation, aiming to assess their therapeutic potential and predict their biological activities. Screening results revealed significant interactions between the compounds and key protein structures, including IGFBP, PI3K, LE, JAK3, and PTP-2, which are involved in critical cellular processes. Furthermore, in silico evaluations were conducted to analyze the physicochemical properties, pharmacokinetics, and toxicological profiles of synthesized compounds.

Insights into the role of potent thiadiazole based Schiff base derivatives in targeting type-II diabetes: A combine in-vitro and in-silico approaches

A novel series of varied substituted thiadiazole based Schiff base analogues (1–21) were designed and characterized using NMR (13C, 1H) and HREI-mass spectrometry, and secerned against the enzymes responsible for hyperglycemia i-e α-amylase and α-glucosidase. Newly designed analogues demonstrated distinct inhibitory activities having IC50= 1.10 ± 0.50 to 21.40 ± 0.20 µM (for alpha-amylase) and 2.50 ± 0.05 to 21.40 ± 0.10 µM (for alpha-glucosidase) in contrast to acarbose a well-known marketed drug (IC50 = 3.16 ± 0.22 & 4.8 ± 0.21 µM for α-amylase and α-glucosidase, respectively). Compound (20) with tri-fluoromethyl at para position of aromatic ring revealed as lead candidate among the members of synthesized series, having effective inhibitory activity against enzymes α-amylase and α-glucosidase. The excellent activity of compound (20) might be due to involvement of fluoro atom interacting via H-bonding with the active sites of enzymes α-amylase and α-glucosidase being targeted. Furthermore, for exploration of binding interactions of potent drugs, molecular docking was performed. For investigation of drug likeness and toxicity, ADME analysis was also conducted.