Salicylaldehyde Moiety Research Articles

The Anti-Cancer Stem Cell Properties of Copper(II)-Terpyridine Complexes with Attached Salicylaldehyde Moieties.

We report the synthesis, characterisation, and anti-breast cancer stem cell (CSC) properties of two copper(II)-terpyridine complexes with bidentate salicylaldehyde moieties (2-hydroxybenzaldehyde for 1 and 2-hydroxy-1-naphthaldehyde for 2). The copper(II)-terpyridine complexes 1 and 2 are stable in biologically relevant aqueous solutions and display micromolar potency towards breast CSCs. The most effective complex 1 is 5-fold and 6.6-fold more potent towards breast CSCs than salinomycin and cisplatin, respectively. The copper(II)-terpyridine complexes 1 and 2 also decrease the formation and viability of three-dimensionally cultured mammospheres within the micromolar range. Notably complex 1 is up to 7-fold more potent towards mammospheres than salinomycin or cisplatin. Mechanistic studies suggest that the copper(II)-terpyridine complexes 1 and 2 are able to readily enter breast CSCs, elevate intracellular reactive oxygen species levels, induce DNA damage (presumably by oxidative DNA cleavage), and evoke apoptosis that is independent of caspases. This study shows that the copper(II)-terpyridine motif is a useful building block for the design of anti-breast CSC agents and reinforces the therapeutic potential of copper coordination complexes.

Synthesis, spectroscopic analysis, molecular docking and DFT study of novel 1,2,3-Triazole derivatives incorporating paramethoxythymol and salicylaldehyde moieties

This study investigates the synthesis, characterization, and computational analysis of novel paramethoxythymol-1,2,3-triazole derivatives derived from naturally occurring thymol. HRMS and NMR spectroscopy (1H and 13C) were meticulously employed to ensure precise identification of the synthesized compounds. Density functional theory (DFT) calculations were performed to elucidate the stability of the derivatives. In silico docking simulations, molecular dynamics, and ADMET analysis provided insights into the potential interactions between the synthesized molecules and the active sites of Epidermal Growth Factor Receptor (EGFR) and B-cell lymphoma 2 (Bcl2). Docking analysis revealed favorable binding affinities of the 1,2,3-triazole derivatives towards EGFR, with compound 5b exhibiting the most potent interaction, characterized by a docking score of -28.8 kJ/mol. Conversely, compound 6b demonstrated a docking score of -29.2 kJ/mol with Bcl2. Molecular dynamics investigations indicated that the complex between Bcl2 and compound 5b is more stable, suggesting it as a potential candidate for inhibiting Bcl2 protein. These findings suggest that paramethoxythymol-1,2,3-triazole derivatives hold promise as lead candidates for the development of novel targeted anticancer agents.

Positional heterogenization effect in salicylaldimine nickel catalyzed ethylene polymerization

Positional heterogenization effect in salicylaldimine nickel catalyzed ethylene polymerization

The first double-armed salamo-like trinuclear Ni(II) complex: Synthesis, structure, spectroscopic and theoretical studies, and fluorescence properties

The first double-armed salamo-based tri-nuclear Ni(II) complex, named as [Ni3(L)(μ2-OAc)2]·3CHCl3 was successfully self-assembled, and elucidated via elemental analyses, spectroscopic technology and theoretical analyses. The results indicated that one ligand H4L has coordinated with three Ni(II) atoms in a 1:3 ratio unreported previously. One of the three Ni(II) atoms is located at the cavity of the N2O2 donor, while other two Ni(II) atoms are sited at the NO2 cavities formed by double-armed salicylaldehyde moieties, respectively, and further coordinated via two bridging μ2-acetate groups, which is a quite novel structure. The fluorescent properties and a range of theory calculations in the ligand and its Ni(II) complex were researched in detail.

Synthesis of chiral salen-MnIII complexes tagged with ionic liquid as recoverable homogeneous catalysts for the oxidative kinetic resolution of (±)-secondary alcohols

New chiral salen ligands tagged with imidazolium based ionic liquids (ILs) were synthesized from the 5-bromopentyl benzoate functionality at C-5 position of salicylaldehyde moiety, N-methylimidazole, and (1R,2R)-1,2-diphenylethane-1,2-diamine/(1R,2R)-cyclohexane-1,2-diamine in 81–92% yields. The chiral salen ligands were further reacted with Mn(OAc)2.4H2O in dry methanol under N2 atmosphere, followed by air oxidation with LiCl to produce the IL tagged chiral salen-MnIII complexes 1(a–c) and 2(a–c) in 79-86% yields. The catalytic activities of these complexes were evaluated in the oxidative kinetic resolution of (±)-1-phenylethanol (8a) with N-bromosuccinimide (NBS) as an oxidizer in biphasic solvent system [H2O - organic solvent (2: 1, v/v)] at 0 °C. The enantioselective oxidation of various (±)-secondary alcohols catalyzed by complex 1c (1 mol%) afforded the chiral secondary alcohols with up to 99% enantiomeric excess and 29.6 krel (selectivity factor) value. The IL tagged chiral salen-MnIII complex 1c was easily recovered with hexane and subsequently reused for five recycles with no significant loss in conversion of (±)-1-phenylethanol (8a) and ee of the resolved product.

Synthesis, characterization, molecular docking, ADMET prediction, and anti-inflammatory activity of some Schiff bases derived from salicylaldehyde as a potential cyclooxygenase inhibitor

A series of Schiff base-bearing salicylaldehyde moiety compounds (1-4) had been designed, synthesized, subjected to insilico ADMET prediction, molecular docking, characterization by FT-IR, and CHNS analysis techniques, and finally to their Anti-inflammatory profile using cyclooxygenase fluorescence inhibitor screening assay methods along with standard drugs, celecoxib, and diclofenac. The ADMET studies were used to predict which compounds would be suitable for oral administration, as well as absorption sites, bioavailability, TPSA, and drug likeness. According to the results of ADME data, all of the produced chemicals can be absorbed through the GIT and have passed Lipinski’s rule of five. Through molecular docking with PyRx 0.8, these synthesized compounds were tested insilico selectivity toward COX-1 and COX-2 and in vitro for their anti-inflammatory efficacy . In vitro testing demonstrated that all of the produced compounds had significantly stronger activity against the COX-2 enzyme than COX-1. Among these, compound 1 displayed the most potent inhibitory activity with an IC50 value of 0.19 µM compared to standard drug celecoxib (IC50 = 0.29 µM). The most active derivative compound1 was oriented towards the active site and occupied the target enzyme based on the docking investigation against COX-1 and COX-2. In addition, insilico investigations found that COX-2 has a higher inhibitory activity than COX-1

Near-infrared rhodol dyes bearing salicylaldehyde moieties for ratiometric pH sensing in live cells during mitophagy and under hypoxia conditions.

We describe a simple but efficient approach to make fluorescent probes A and B based on rhodol dyes incorporated with salicyaldehyde moiety for monitoring pH changes in mitochondria under oxidative stresses and hypoxia conditions, and for tracking mitophagy processes. Probes A and B possess pKa values (pKa ≈ 6.41 and 6.83 respectively) near physiological pH and exhibit decent mitochondria-targeted capabilities, low cytotoxicity, and useful ratiometric and reversible pH responses, which make the probes appropriate for monitoring pH fluctuations of mitochondria in living cells with built-in calibration feature for quantitative analysis. The probes have been effectively useful for the ratiometric determination of pH variations of mitochondria under the stimuli of carbonyl cyanide-4(trifluoromethoxy)phenylhydrazone (FCCP), hydrogen peroxide (H2O2), and N-acetyl cysteine (NAC), and during mitophagy triggered by cell nutrient deprivation, and under hypoxia conditions with cobalt chloride (CoCl2) treatment in living cells. In addition, probe A was efficient in visualizing pH changes in the larvae of fruit flies.

A series of 1,2,3-triazole compounds: Synthesis, characterization, and investigation of the cholinesterase inhibitory properties via in vitro and in silico studies

A series of 1,2,3-triazole compounds derived from a salicylaldehyde moiety were synthesized in high yields using copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. The structures of the newly synthesized 1,2,3-triazole compounds were characterized by FT-IR, NMR, and HRMS analyses. The inhibitory activities of all the target compounds were investigated against electric eel acetylcholinesterase (eeAChE) and equine serum butyrylcholinesterase (eqBChE) enzymes. The activity results were compared with galantamine used as a reference compound. The in vitro biological assays showed that most of the target compounds had quite good inhibition activities for eeAChE, while weaker towards eqBChE. Among them, compound 23f exhibited better activity than both other target compounds and galantamine against both eeAChE (IC50: 0.458 µM) and eqBChE (IC50:1.721 µM). Molecular docking studies of all target compounds were performed on the 3D crystallographic structures of eeAChE, Homo sapiens AChE, and BChE enzymes. The binding energies appear to be consistent with the activity results. Moreover, it was determined that 23f interacted with crucial residues of the catalytic active site (CAS) and peripheral anionic site (PAS) of both AChE and BChE due to its dual binding feature. Finally, in silico ADME and toxicity properties of the compounds were investigated using the Swiss ADME and ProTox-II websites. The compounds have appropriate drug-likeness scores, Additionally, it has been estimated that 23f, the most active compound, and 23c are within the best limits in terms of oral bioavailability and exhibit low levels of toxicity. Consequently, the target compounds, especially 23f, can be considered promising inhibitors for the cholinesterase enzymes.

Family of Well-Defined Chiral-at-Cobalt(III) Complexes as Metal-Templated Hydrogen-Bond-Donor Catalysts: Effect of Chirality at the Metal Center on the Stereochemical Outcome of the Reaction.

A family of well-defined Λ- and Δ-diastereomeric octahedral cationic chiral-at-cobalt complexes were obtained by a simple two-step reaction of (R,R)-1,2-diaminocyclohexane, (R,R)-1,2-diphenylethylenediamine, or (S)-2-(aminomethyl)pyrrolidine and substituted salicylaldehydes with a cobalt(III) salt. It was observed for the first time that the use of an excess of cobalt(III) salt provides both the enantiopure Λ and Δ forms of the corresponding cobalt(III) complexes 1 and 2 in a ratio of diastereomers ranging from 1:1.6 to >20:1 (Λ/Δ) and in 31-95% combined yields. The obtained complexes were robust, air- and bench-stable, soluble in most of organic solvents, and insoluble in water. Through variation of the substituents in the phenyl ring of the salicylaldehyde moiety, it was shown that both steric and electronic effects of substituents have a significant impact on the formation of Λ and Δ isomers. Next, the efficacies of the enantiopure metal-templated complexes 1-3 were investigated in three benchmark asymmetric reactions in order to compare their catalytic activity. The chiral cobalt(III) complexes 1-3 were tested as enantioselective hydrogen-bond-donor catalysts in such important reactions as the Michael addition of the O'Donnell substrate to methyl acrylate, epoxidation of chalcone, and trimethylsilylcyanation of benzaldehyde. It was clearly demonstrated that the chirality at the cobalt center has an impact on the stereochemical outcome of the reactions. In particular, the Λ(R,R)-1 and Δ(R,R)-1 complexes acted as "pseudoenantiomeric" catalysts in the epoxidation and trimethylsilylcyanoation reactions, providing both enantiomers of the products with up to 57% enantiomeric excess.

N-diethylaminosalicylidene based “turn-on” fluorescent Schiff base chemosensor for Al3+ ion: Synthesis, characterisation and DFT/TD-DFT studies

A Schiff base chemosensor (H3L) based on the 4-(N,N-Diethylamino)salicylaldehyde moiety has been synthesized and characterized using several spectroscopic techniques i.e. 1H-NMR, FT-IR, Mass and UV-visible. The chemosensor shows high selectivity for Al3+ ion through ‘turn-on’ cyan colour fluorescence over a variety of metal ions i.e. Ni2+, Zn2+, Cd2+, Mn2+ ions except Co2+, Cu2+ and Fe3+ ions. The chemosensor exhibits 20 fold intensity enhancement at 481 nm (λex = 378 nm) against Al3+ ion until saturation point. Additionally, the detection limit and stability constant were found to be 1.2 × 10−6 M and 5.2 × 105 M−1, respectively with the low equivalent range of 1–34 µM. The chemosensor also displays similar fluorescence behaviour for Al3+ ion in a variety of solvents and solvent mixtures. The quantum yield (ФF) values for H3L and Al3+–complex were observed to be 0.08 and 0.29, respectively. The Job's plot calculations show that, H3L binds to Al3+ ion in 2:1 ratio. 1H-NMR titration analysis indicates that the chemosensor undergoes mono-deprotonation while binding to Al3+ ion. The geometry of the chemosensor and Al3+–complex were optimised and some thermodynamic parameters were calculated using Density Functional Theory (DFT). The Gibbs free energy of complex was calculated to be -1272.00 kcal/mol. Further, the optical and electronic properties of the proposed complex were explained with the help of Time Dependent-Density Functional Theory (TD–DFT).

Synthesis and characterization of new metal complexes containing Triazino[5,6–b]indole moiety: In vitro DNA and HSA binding studies

The present study reports the synthesis, structural characterization of Ni(II) (1,3) and Cu(II) (2,4) metal complexes of Schiff-base (L) derived from 5H-[1,2,4]triazino[5,6-b]indol-3-amine and salicylaldehyde moiety. The coordination sphere of Cu(II)/Ni(II) was completed by tethering secondary ligand 2,2′–Bipyridine and 1,10 phenanthroline to obtain the final complexes 1–4, respectively. The spectral analysis of complexes 1 and 3 suggested square planar geometry while complexes 2 and 4 acquire the octahedral geometry around the metal centers. In vitro DNA binding profiles of the newly synthesized metal complexes 1–4 with calf thymus DNA (CT DNA) were explored by employing electronic absorption titrations and fluorescence spectral studies. The results revealed that complexes 1–4 bind to DNA through electrostatic surface binding mode along with partial intercalation in the minor groove. Moreover, complexes 3 and 4 have stronger DNA binding propensity with higher intrinsic binding constant Kb values of 1.9 × 104 and 4.8 × 104 M–1, respectively. Additionally, HSA binding studies of ligand L and metal complexes 1–4 support the static quenching mechanism and alterations in the microenvironment around Trp–214 residues causing conformational distortions in the HSA secondary structure. Furthermore, molecular docking studies of complexes 3 and 4 with DNA and HSA confirms that both specifically binds in G–C rich regions of the DNA minor groove and subdomain IIA pocket of HSA near the Trp–214 residue.

A Reagent for Amine‐Directed Conjugation to IgG1 Antibodies

AbstractFunctionalized antibodies are an indispensable resource for diagnosis, therapy and as a research tool for chemical biology. However, simpler and better methodologies are often required to improve the labeling of antibodies in terms of selectivity and scalability. Herein, we report the development of an easily available chemical reagent that allows site‐directed labeling of native human IgG1 antibodies in good yield and mono‐labeling selectivity. The salicylaldehyde moiety of the reagent reacts with surface exposed lysine residues to transiently form an iminium ion, and this positions a semi‐reactive ester in proximity of a second lysine residue that reacts with the ester to form an amide. Interestingly, it appears that the formation of the iminium ion also has a significant activating effect of the ester. We use flow cytometry and bio‐layer interferometry to confirm that the labeled antibodies retain antigen binding.

A Reagent for Amine-Directed Conjugation to IgG1 Antibodies.

Functionalized antibodies are an indispensable resource for diagnosis, therapy and as a research tool for chemical biology. However, simpler and better methodologies are often required to improve the labeling of antibodies in terms of selectivity and scalability. Herein, we report the development of an easily available chemical reagent that allows site-directed labeling of native human IgG1 antibodies in good yield and mono-labeling selectivity. The salicylaldehyde moiety of the reagent reacts with surface exposed lysine residues to transiently form an iminium ion, and this positions a semi-reactive ester in proximity of a second lysine residue that reacts with the ester to form an amide. Interestingly, it appears that the formation of the iminium ion also has a significant activating effect of the ester. We use flow cytometry and bio-layer interferometry to confirm that the labeled antibodies retain antigen binding.

Metal-dependent selective formation of calix[4]arene assemblies based on dynamic covalent chemistry.

The reaction of calix[4]arene derivatives 1a and 1b bearing four salicylaldehyde moieties with 1,3-propanediamine gave macrocyclic trimers 5a and 5b, respectively, which have intramolecular bridges formed via the flattened cone conformation. In contrast, a capsular-shaped dimeric cage [7a·2Na]2+ was selectively formed when the conformation of the calix[4]arene moiety of 1a was fixed in the spread cone conformation by complexation with Na+ at the lower-rim amide groups.

A bifunctional optical probe based on ESIPT-triggered disalicylaldehyde with ratiometric detection of iron and copper ions

In this paper, we design and synthesize an N-linked disalicylaldehyde H2Qj1 based on the economical substrates, and it is composed of two identical salicylaldehyde moieties with the intramolecular ESIPT character. During the process of sensing heavy metal ions, it is found that the ESIPT state of H2Qj1 can be rapidly (60 s) destroyed by Fe(III) and Cu(II), resulting in the turn-off fluormetric and colorimetric responses. Serial fluorescence and absorption titration experiments reveal that the H2Qj1-Fe(III) and H2Qj1-Cu(II) sensing systems are ratiometric and their corresponding coordination modes are 1:1 and 2:1. Especially, their LOD values are as low as 0.40 μΜ and 0.21 μΜ which are comparable to reported examples. Moreover, we also develop a convenient technique to detect Fe(III) and Cu(II) using paper-based sensing devices together with smartphone-based RGB analysis method which will rapidly provide the precise determination results, even in the tap water sample. Therefore, this bifunctional disalicylaldehyde H2Qj1 is taken as a useable platform to monitor Fe(III) and Cu(II) and offers some valuable lights for further optical probes.

Mechanistic Studies Inform Design of Improved Ti(salen) Catalysts for Enantioselective [3 + 2] Cycloaddition.

Ti(salen) complexes catalyze the asymmetric [3 + 2] cycloaddition of cyclopropyl ketones with alkenes. While high enantioselectivities are achieved with electron-rich alkenes, electron-deficient alkenes are less selective. Herein, we describe mechanistic studies to understand the origins of catalyst and substrate trends in an effort to identify a more general catalyst. Density functional theory (DFT) calculations of the selectivity determining transition state revealed the origin of stereochemical control to be catalyst distortion, which is largely influenced by the chiral backbone and adamantyl groups on the salicylaldehyde moieties. While substitution of the adamantyl groups was detrimental to the enantioselectivity, mechanistic information guided the development of a set of eight new Ti(salen) catalysts with modified diamine backbones. These catalysts were evaluated with four electron-deficient alkenes to develop a three-parameter statistical model relating enantioselectivity to physical organic parameters. This statistical model is capable of quantitative prediction of enantioselectivity with structurally diverse alkenes. These mechanistic insights assisted the discovery of a new Ti(salen) catalyst, which substantially expanded the reaction scope and significantly improved the enantioselectivity of synthetically interesting building blocks.

Synthesis, Structures, and Single-Molecule Magnetic Properties of Three Dy2 Complexes.

To explore the influences of the subtle structural variations in the ligand backbones on the single-molecule magnetic properties of dinuclear dysprosium(III) complexes, three ligands-H2 L1 (H2 L1 =N1 ,N3 -bis(salicylaldehyde)diethylenetriamine), H2 L2 (H2 L2 =N1 ,N3 -bis(3-methoxysalicylidene)diethylenetriamine), and H2 L3 (H2 L3 =N1 ,N3 -bis(5-chlorosalicyladehyde)diethylenetriamine)-were synthesized and employed to prepare the expected dinuclear dysprosium(III) complexes. The three ligands differ in terms of the substituents at the benzene rings of the salicylaldehyde moieties. The reactions of Dy(NO3 )3 ⋅6 H2 O, pivalic acid, and the ligands H2 L1 , H2 L2 , and H2 L3 generated complexes with the formulae [Dy2 (L1 )2 (piv)2 ] (1), [Dy2 (L2 )2 (piv)2 ] (2), and [Dy2 (L3 )2 (piv)2 ]⋅ 2 MeCN (3), respectively. The purposeful attachment of the functional groups with varied sizes at the benzene rings of the salicylaldehyde backbones resulted in slight differences in the Dy-O-Dy bond angles and the Dy⋅⋅⋅Dy bond lengths in 1-3; consequently, the three complexes exhibited distinct magnetic properties. They all showed slow magnetization relaxation with energy barriers of 40.32 (1), 31.67 (2), and 33.53 K (3). Complete active space self-consistent field (CASSCF) calculations were performed on complexes 1-3 to rationalize the slight discrepancy observed in the magnetic behavior. The calculated results satisfactorily explained the experimental outcomes.

Low-cost Schiff bases chromophores as efficient co-sensitizers for MH-13 in dye-sensitized solar cells

Herein, we reported on the synthesis of four Schiff bases (S1–4) based on salicylaldehyde moieties and their applications as metal-free organic chromophores for sensitization and co-sensitization of dye-sensitized solar cells (DSSCs). These sensitizers are comprised of a phenyl ring as a donor scaffold connected with a carboxylic group as acceptor/anchoring unit. To gauge their applicability as photosensitizers for DSSCs the photophysical, electrochemical, theoretical studies and charge transport characteristics were carried out. Interestingly, uses of S2 and S4 dyes as co-sensitizers with well-known MH-13 dye resulted in enhancing its photovoltaic properties from 8.217 to 8.79% and 8.48%, respectively. Furthermore, the photo-sensitizer S3 individually shows better photovoltaic properties compared to S1, S2 and S4, due to the fast photo-induced electron transfer from the phenyl ring to the nitro group. This fast electron transfer resulted from the overlapping between HOMO and LUMO levels on phenyl ring bearing nitro group. The results indicate that these simple and easy prepared Schiff bases moieties may be considered as promising and low-cost co-sensitizers for DSSCs.

Highly selective and sensitive turn-on fluorescent probes for sensing Hg2+ ions in mixed aqueous solution

A highly selective and sensitive probe 1b was successfully developed for detecting Hg2+ ions in mixed aqueous medium with a “turn on” fluorescence mode, via a series of structural optimization of probes. These probes could be easily synthesized by one-step condensation reactions between o-phenylenediamine or 2, 3-diaminonaphthalene and o (salicylaldehyde), m, or p-hydroxybenzaldehyde. Introducing a certain amount of Hg2+ ions the fluorescence of probes bearing one or two salicylaldehyde moieties including probes 1a, 1b, and 4 could be turned on. The fluorescent response is likely due to the well matching between Hg2+ ions size and the geometric structure of probes, resulting in that probes bearing salicylaldehyde moiety are mostly favorable for binding with Hg2+ ions by way of 1:1 molar ratio. These bindings likely facilitate excited state internal proton transfer (ESIPT) or ESIPT coupled aggregation-induced enhancement of emission (AIEE) process. Considering the sensitivity and the potential of practical application, probe 1b was chosen to establish a fluorescent enhancement sensing system towards Hg2+ ions over other competing metal ions, with excellent limit of detection of 12.5 ppb.

The metal-nonoate Ni(SalPipNONO) inhibits in vitro tumor growth, invasiveness and angiogenesis.

Nitric oxide (NO) exerts conflicting effect on tumor growth and progression, depending on its concentration. We aimed to characterize the anti-cancer activity of a new NO donor, Ni(SalPipNONO) belonging to the class of metal-nonoates, in epithelial derived tumor cells, finally exploring its antiangiogenic properties. Tumor epithelial cells were screened to evaluate the cytotoxic effect of Ni(SalPipNONO), which was able to inhibit cell proliferation in a dose dependent manner, being more effective than the commercial DETA/NO. The human lung carcinoma cells A549 were chosen as model to study the anti-cancer mechanisms exerted by the compound. In these cells, Ni(SalPipNONO) inhibited clonogenicity and cell invasion, while promoting apoptosis. The antitumor activity was partly due to NO-cGMP dependent pathway, contributing to reduced cell number and apoptosis, and partly to the salicylaldehyde moiety and reactive oxygen species (ROS) activated ERK1/2 signaling converging on p53 dependent caspase-3 cleavage. An additional contribution by downstream cycloxygenase-2 (COX-2) derived cyclopentenones may explain the tumor inhibitory activities. As NO has been described to affect tumor angiogenesis, we checked this activity both on tumor and endothelial cell co-cultures and in Matrigel in vivo assay. Our data document that Ni(SalPipNONO) was able to both reduce angiogenic factor expression by tumor cells acting on hypoxia inducible factor-1α (HIF-1 α) level, and endothelial cell functions related to angiogenesis. Collectively, these data confirm the potential use of NO donors and in particular Ni(SalPipNONO) acting through multiple mechanisms, as an agent to be further developed to be used alone or in combination with conventional therapy.