Salicylaldehyde Benzoylhydrazone Research Articles

A salicylaldehyde benzoyl hydrazone based near-infrared probe for copper(ii) and its bioimaging applications

Developing highly sensitive and selective methods for Cu2+ detection in living systems is of great significance in clinical copper-related disease diagnosis. In this work, a near infrared (NIR) fluorescent probe, CySBH, with a salicylaldehyde benzoyl hydrazone group as a selective and sensitive receptor for Cu2+ was designed and synthesized. The specific coordination of the salicylaldehyde benzoyl hydrazone group in CySBH with Cu2+ can induce a distinct quench of the fluorescence intensity, allowing for real-time tracking of Cu2+. We have demonstrated that CySBH could rapidly recognize Cu2+ with good selectivity and high sensitivity. Moreover, on the basis of low cell cytotoxicity, the probe was used to visualize Cu2+ in two cell lines by fluorescence imaging. Furthermore, CySBH can also be used to monitor Cu2+in vivo due to its NIR emission properties. These overall results illustrate that the NIR fluorescent probe CySBH provides a novel approach for the selective and sensitive monitoring of Cu2+ in living systems.

In vitro and in silico studies of radical scavenging activity of salicylaldehyde benzoylhydrazones

Hydrazones are key compounds for drug design and popular building blocks in the development of functional materials because of their simple structure, straightforward synthesis, hydrolytic stability, tendency toward crystallinity and tunable properties, etc. Hydrazones have been under study for a long time, but many of their electronic and structural properties (that can be attributed to the basic system structure) remain unexplored. In this paper the effect of substitution is studied for a set of selected aroylhydrazones – derivatives of the active chelator salicylaldehyde benzoyl hydrazone (SBH). The molecular structure of the compounds in nonpolar and polar media was characterized by DFT computations and vibrational (ATR-FTIR and Raman) spectroscopy. The radical scavenging ability of the compounds was tested towards stable free radicals as well as for inhibiting the iron induced oxidative stress in a lecithin containing model system. The possible mechanisms of antioxidant action were evaluated by DFT calculations in polar and nonpolar media. The most reactive sites for hydrogen atom abstraction and proton transfer were determined based on the calculated enthalpies required for the formation of hydroxyl and amide radicals and ionic species. The structural parameters and thermodynamic data for the studied compounds were correlated with the observed effects in the in vitro model systems in order to rationalize the influence of the nature and position of the substituent in the phenyl ring on the antioxidant properties.

A highly sensitive and selective spectrophotometric method for the determination of vanadium at nanotrace levels in some environmental, biological, soil, food, and pharmaceutical samples using salicylaldehyde-benzoylhydrazone

A very simple, non-extractive and new spectrophotometric method for the swift determination of trace amount of vanadium using salicylaldehyde-benzoylhydrazone (Sal-BH) has been developed. Sal-BH undergoes a reaction in a slightly acidic solution (0.0016-0.0032 M H2S04) with vanadium to give a light greenish-yellow chelate, which has an absorption maximum at 392 nm. The reaction is instantaneous and absorbance remains stable for over 24 hrs. The average molar absorption co-efficient and Sandell’s sensitivity were found to be 2.5039×105 L/mol.cm and 1.0 ng/cm2 V, respectively. Beer’s law was obeyed for 0.001-30 mg/L of V, providing a detection limit of 0.1 µg/L of V and RSD 0-2 %. The stoichiometric composition of the chelate is 1:1 (V:Sal-BH). Interference study shows that a large excess of over 60 cations, anions, and some common complexing agents (such as chloride, azide, tartrate, EDTA and SCN‑, etc.) satisfy the tolerance limit. The developed method was successfully used in the determination of vanadium in several standard reference materials as well as in some environmental waters, biological fluids, soil, food and pharmaceutical samples and solutions containing both vanadium (IV) and vanadium (V). The results of the proposed method for assessing biological, food and vegetable samples were comparable with ICP-OES and AAS were found to be in excellent agreement. The method has high precision and accuracy (s = ±0.01 for 0.5 mg/L).

A highly sensitive and rapid spectrophotometric method for the determination of molybdenum at nano-trace levels in some real, environmental, biological, food and soil samples using salicylaldehyde-benzoylhydrazone

A very simple, sensitive and highly selective non-extractive new spectrophotometric method has been developed for the determination of molybdenum at nano-trace levels using salicylaldehyde-benzoylhydrazone (Sal-BH). The method is based on the reaction of non-absorbent Sal-BH in a slightly acidic solution (0.0025-0.0075 M H2S04) with molybdenum (VI) to give a light yellowish chelate, which has an absorption maximum at 440 nm. The reaction is instantaneous and absorbance remains stable for over 24 h. The average molar absorption coefficient and Sandell’s sensitivity were found to be 4.32×105 L/mol.cm and 5 ng/cm2 of molybdenum, respectively. Linear calibration graphs were obtained for 0.01-60.00 mg/L of molybdenum having detection limit of 1 µg/L and RSD 0.0-2.0 %. The stoichiometric composition of the chelate is 1:1 (Mo:Sal-BH). A large excess of over 60 cations, anions and some common complexing agents (such as chloride, azide, tartrate, EDTA, SCN- etc.) do not interfere in the determination. The method was successfully used in the determination of molybdenum in several Certified Reference Materials (Alloys, steels, water, hair and bovine liver) as well as in some environmental waters (Potable and polluted), biological samples (Human blood, urine, nails, hair, food and vegetables), soil samples, and solutions containing both molybdenum(VI) and molybdenum(V) as well as complex synthetic mixtures. The results of the proposed method for assessing biological, food and vegetables samples were found to be in excellent agreement with those obtained by ICP-OES and AAS. The method has high precision and accuracy (s = ±0.01 for 0.5 mg/L).

3-methoxy aroylhydrazones – free radicals scavenging, anticancer and cytoprotective potency

ABSTRACTObjective: This study aimed to determine the capability of newly designed 3-methoxy derivatives of salicylaldehyde benzoylhydrazone to influence the oxidative stress processes and to test their in vitro cytotoxicity.Methods: We have used chemiluminescent and spectrophotometric model systems containing different types of reactive oxygen species (OH●, OCl─ and O2─●). The hydrazones effect on the viability of Hep-G2, HEK-293 and SH-SY5Y cell lines was determined via MTT assay.Results: The comparative analysis of the C50 values of the chemiluminescent investigation demonstrated moderate activity against the hydroxyl radicals (C50 > 50 μmol/L) and remarkable reactivity in the systems containing a superoxide radical and a hypochlorous anion (C50 < 3.7 μmol/L). Further experiments in the spectrophotometric system of UV-induced OH● generation and consequent 2′-deoxyribose oxidative damage excluded the possibility of quenching effect and proved the direct interaction of the studied compounds with that generated in the system reactive oxygen species (ROS). The encapsulation of the studied derivatives into chitosan-alginate particles led to the protection and stabilization of their antioxidant activity as revealed by a one-month study using the ABTS ●+ method. The cytotoxic study revealed less pronounced effects against the non-malignant cell line (HEK-293) compared to Hep-G2 and SH-SY-5Y cells.Discussion: The incorporation of a hydroxyl group in the hydrazide part of a parent molecule which relates to better antioxidant effect in most of the studied systems is associated with higher IC50 values in all cytotoxicity experiments and relates to the cytoprotective effect against N-methyl-D-aspartate-induced excitotoxicity in SH-SY5Y human neuronal cells.

Solid phase extraction of Cu (II), Ni (II), Co (II), and Fe (III) ions in water samples using salicylaldehyde benzoylhydrazone on Amberlite XAD-4 and their determinations by flame atomic absorption spectrometry

A multi element preconcentration procedure for solid phase extraction on Amberlite XAD-4 as their salicylaldehyde benzoylhydrazone chelates and flame atomic absorption spectrometric determination of some trace metal ions in water samples are proposed in this work. The influences of some analytical parameters, including pH of aqueous solution, amounts of reagent, flow rates of sample and eluent solutions, and sample volume on the quantitative recoveries of copper, nickel, cobalt, and iron were investigated. The effects of concomitant ions on the retentions of the analytes were also examined. The developed method has been successfully applied to the determination of metal ions in some real samples, including, tap water, river water, spring water, and waste water.

Enhancing the copper(II) complexes cytotoxicity to cancer cells through bound to human serum albumin

We use Schiff-base salicylaldehyde benzoylhydrazone (HL) as the ligand for copper(II), resulting in the complexes [CuCl(L)]·H2O (C1), [CuNO3(L)]·H2O (C2) and [CuBr(L)]2 (C3). We characterize the Cu(II) compounds' interactions with human serum albumin (HSA) using fluorescence spectroscopy and molecular docking. These studies revealed that Cu(II) compounds propensity bound to IIA subdomain of HSA possible by hydrophobic interactions and hydrogen bond. Cu(II) compounds produce intracellular reactive oxygen species (ROS) in cancer cells. Complexes of HSA and copper(II) compounds enhance about 2-fold cytotoxicity in cancer cells but do not raise cytotoxicity levels in normal cells in vitro. Compared with C3 alone, HSA–C3 complex promotes HepG2 cell apoptosis and has a stronger capacity to promote cell cycle arrest at the G2/M phase of HepG2.

Forced solid-state interactions for the selective "turn-on" fluorescence sensing of aluminum ions in water using a sensory polymer substrate.

Selective and sensitive solid sensory substrates for detecting Al(III) in pure water are reported. The material is a flexible polymer film that can be handled and exhibits gel behavior and membrane performance. The film features a chemically anchored salicylaldehyde benzoylhydrazone derivative as an aluminum ion fluorescence sensor. A novel procedure for measuring Al(III) at the ppb level using a single solution drop in 20 min was developed. In this procedure, a drop was allowed to enter the hydrophilic material for 15 min before a 5 min drying period. The process forced the Al(III) to interact with the sensory motifs within the membrane before measuring the fluorescence of the system. The limit of detection of Al(III) was 22 ppm. Furthermore, a water-soluble sensory polymer containing the same sensory motifs was developed with a limit of detection of Al(III) of 1.5 ppb, which was significantly lower than the Environmental Protection Agency recommendations for drinking water.

Synthesis and Characterization of Copper Complex of Salicylaldehyde Benzoyl Hydrazone

Copper complex of type [Cu(SBH)2] was synthesized and characterized by different analytical procedure and spectral studies. The complex was insoluble in common organic solvents and it has melting point in between 254-258°C. Infrared spectrum showed the bonding through enolic oxygen and azomethine nitrogen. The electronic spectral studies showed that the Cu(II) is in tetrahedral coordination environment. DOI: http://dx.doi.org/10.3126/jncs.v29i0.9231Journal of Nepal Chemical SocietyVol. 29, 2012Page: 11-17Uploaded date : 12/3/2013

DNA-binding studies of two dioxomolybdenum(VI) complexes of salicylaldehyde benzoylhydrazone ligands

The reaction of [MoO2(acac)2] with salicylaldehyde benzoylhydrazone (H2L1) and with one of its derivatives (H2L2) resulted in the production of two neutral mononuclear dioxomolybdenum complexes; MoO2L1(MeOH) 1 and MoO2L2(MeOH) 2, respectively. (H2L1) was derived from the reaction of benzhydrazide and 2-hydroxybenzaldehyde (salicylaldehyde) and (H2L2) was derived from the reaction of benzhydrazide and 2-hyroxy-3-methoxybenzaldehyde. Interactions of the complexes were investigated with calf thymus DNA by UV–Vis, fluorescence and circular dichroism spectroscopies to determine their biological effects. Results evaluated the binding affinity of complexes 1 and 2 to CT-DNA by UV and presented binding constants (Kb) of (3.52±0.1)×103M−1 and (4.49±0.1)×103M−1, respectively. Evaluations of fluorescence approved the binding of the fluorescent complex 2, to DNA. Competitive studies with ethidium bromide (EB) showed that none of the complexes displaced the DNA–EB binding efficiency effectively while they changed the polarity of the environment by occupying the previous place of water molecules around the helix. CD spectral studies revealed that as a result of interaction with both complexes, calf thymus B-DNA turned into A-like structure.According to our results both complexes bind to DNA via a non-intercalative mode, presumably through groove binding.

Structural requirements of salicylaldehyde benzoylhydrazones and their Cu(II) complexes for anticancer activity

Salicylaldehyde benzoylhydrazone (H2sb) has a variety of biological activities including anticancer activity. The Cu(II) complexes of H2sbs possess enhanced anticancer activity as compared with their free ligands. A quantitative structure–activity relationship (QSAR) analysis was performed on a series of H2sb ligands and their corresponding Cu(II) complexes to capture the structural requirements that are responsible for the bioactivity. The predictive QSAR models were developed using statistical techniques such as multiple linear regression (MLR) and principal component regression analysis (PCRA). We used different combinations of various descriptors such as a physicochemical descriptor, electrotopological state atom (ETSA) indices, and descriptors derived from density functional theory (DFT) calculations. The DFT-derived descriptors used for QSAR analysis are HOMO and LUMO energies, atomic charges, chemical potential, and hardness. Our developed models showed the importance of the lipophilicity index (ClogP), ETSA indices, and atomic charges for anticancer activities of the H2sb analogs and their Cu(II) complexes. In addition, our MLR models revealed that, while the global lipophilicity index and hardness are important for anticancer activity of H2sb ligands, chemical potential and HOMO energy are important for the anticancer activity of Cu(II) complexes.

ChemInform Abstract: Synthesis, Characterization and Cytotoxic Activity of New Salicylaldehyde Benzoylhydrazone Derivatives as Potential Antiproliferative Agents.

AbstractThe cytotoxic effects of new hydrazones (I) are examined on a wide spectrum of human tumor cell lines.

Synthesis, characterization and cytotoxic activity of new salicylaldehyde benzoylhydrazone derivatives as potential anti-proliferative agents

Three new hydrazones, derivatives of salicylaldehyde benzoylhydrazone, were synthesized as potential anti-proliferative compounds. The structure of the new compounds was characterized by elemental and thermo-gravimetric analyses, IR, 1H and 13C-NMR spectroscopy and quantum chemical calculations. The cytotoxic effects of new hydrazones were examined on a wide spectrum of human tumor cell lines. The obtained results revealed that all compounds proved to be equipotent or moreactive than cisplatin, and far more activethan another utilized anticancer drug, melphalan. On the basis of IC50 values the compound 3-methoxy-salicylaldehyde isonicotinoylhydrazone (mSIH) was found to be the most active cytotoxic agent at all cell lines.

(E)-N′-(5-Chloro-2-oxidobenzylidene-κO)-3,4,5-trimethoxybenzohydrazidato-κ2N′,O](pyridine-κN)copper(II)

In the title compound, [Cu(C17H15ClN2O5)(C5H5N)], the CuII atom is coordinated by one N atom and two O atoms from an anionic salicyl­aldehyde benzoyl­hydrazone ligand and one pyridine N atom in a distorted square-planar geometry. The bonds displays the usual elongation with mean Cu—O and Cu—N bond lengths of 1.926 and 1.976 Å, respectively. The pyridine ring makes dihedral angles of 26.12 (13) and 11.08 (12)°, respectively, with the trimeth­oxy­phenyl and phenolate rings, which make a dihedral angle of 16.05 (12)° with one another.

Development and Applications of Fluorescent Indicators for Mg2+ and Zn2+

In a study of the spectroscopic behavior of two Schiff base derivatives, salicylaldehyde salicylhydrazone (1) and salicylaldehyde benzoylhydrazone (2), Schiff base 1 has high selectivity for Zn(2+) ion not only in abiotic systems but also in living cells. The ion selectivity of 1 for Zn(2+) can be switched for Mg(2+) by swapping the solvent from ethanol-water to DMF (N,N-dimethylformamide)-water mixtures. Imine 2 is a good fluorescent probe for Zn(2+) in ethanol-water media. Many other ions tested, such as Li(+), Na(+), Al(3+), K(+), Ca(2+), Cr(3+), Mn(2+), Fe(3+), Co(2+), Ni(2+), Cu(2+), Ag(+), Cd(2+), Sn(2+), Ba(2+), Hg(2+), and Pb(2+), failed to induce any spectral change in various solvents. The selectivity mechanism of 1 and 2 for metal ions is based on a combinational effect of proton transfer (ESPT), C═N isomerization, and chelation-enhanced fluorescence (CHEF). The coordination modes of the complexes were investigated.

Aerobic epoxidation of olefins over the composite catalysts of Co-ZSM-5(L) with bi-/tridentate Schiff-base ligands

Three tridentate or bidentate Schiff-base ligands inclusive of salicylaldehyde benzoylhydrazone (L1), vanillic aldehyde benzoylhydrazone (L2) and 4-methyl benzaldehyde benzoylhydrazone (L3), have been designed, synthesized and employed to coordinate with Co2+ ions and ion-exchanged Co-ZSM-5 forming several Co-L complexes and Co-ZSM-5(L) composite catalysts. The catalytic epoxidation of several alkenes with dry air has been carried out at 90°C under atmospheric pressure using Co-L complexes and Co-ZSM-5(L) catalysts (using TBHP in small amounts as the initiator). In contrast, the catalysts Co-ZSM-5(L) shows higher catalytic activity than Co-ZSM-5 itself and Co-L complexes. Among three Co-ZSM-5(L) catalysts, Co-ZSM-5(L1) exhibits the highest activity for the selective epoxidation of alkenes. Recycling studies show the recyclability of Co-ZSM-5(L1) as a heterogeneous catalyst, which does not lose the catalytic activity after even eight reuses appreciably. Based on the experiments, one possible reaction mechanism is proposed.

Modifications of boronic ester pro-chelators triggered by hydrogen peroxide tune reactivity to inhibit metal-promoted oxidative stress

Several new analogs of salicylaldehyde isonicotinoyl hydrazone (SIH) and salicylaldehyde benzoyl hydrazone (SBH) that contain an aryl boronic ester (BSIH, BSBH) or acid (BASIH) in place of an aryl hydroxide have been synthesized and characterized as masked metal ion chelators. These pro-chelators show negligible interaction with iron(III), although the boronic acid versions exhibit some interaction with copper(II), zinc(II) and nickel(II). Hydrogen peroxide oxidizes the aryl boronate to phenol, thus converting the pro-chelators to tridentate ligands with high affinity metal binding properties. An X-ray crystal structure of a bis-ligated iron(III) complex, [Fe(SBH(m-OMe)(3))(2)]NO(3), confirms the meridonal binding mode of these ligands. Modifications of the aroyl ring of the chelators tune their iron affinity, whereas modifications on the boron-containing ring of the pro-chelators attenuate their reaction rates with hydrogen peroxide. Thus, the methoxy derivative pro-chelator (p-OMe)BASIH reacts with hydrogen peroxide nearly 5 times faster than the chloro derivative (m-Cl)BASIH. Both the rate of pro-chelator to chelator conversion as well as the metal binding affinity of the chelator influence the overall ability of these molecules to inhibit hydroxyl radical formation catalyzed by iron or copper in the presence of hydrogen peroxide and ascorbic acid. This pro-chelator strategy has the potential to improve the efficacy of medicinal chelators for inhibiting metal-promoted oxidative stress.

Salicylaldehyde Benzoyl Hydrazone: Isomerization Due to Water. A Structural Analysis Using a Combination of NMR, IR, and Theoretical Investigations

Solutions of salicylaldehyde benzoyl hydrazone (SBH) in mixed DMSO/H2O solvents have been studied by IR and NMR spectroscopy. Adding water to dilute solutions in DMSO changes the major conformation from the fully extended E isomer denoted B2E to another E isomer, B1E, where the carbonyl is associated with water. A minor Z form, B2Z, is also detected both in DMSO and in the mixed solvent. Near saturation in the mixed solvent, the major species has an imidinol function and the ratio B2Z/B1E increases. Raising the pH also favors the Z configuration. According to quantum mechanical calculations, the B2Z imidinol or monodeprotonated forms are stabilized by several kcal-mol−1 with respect to their B1E and B2E counterparts, whereas the reverse is true for free or hydrated ketones. Free B2E ketone is calculated to be slightly more stable than its B1E counterpart, but the specific association with water reverses the situation. The balance between B1E, B2E, and B2Z forms appears to depend mainly on steric strain release and on hydrogen bond formation involving either both nitrogens, N1 and N2, of the hydrazone or at least one of them, N1 for the E configuration or N2 for the Z one. Calculation indicates that the first deprotonation occurs at the NH site for the B1E and B2E forms, but at the OH phenol site for B2Z.

Mono‐, Di‐ and Trinuclear Dioxo Complexes of Uranium Containing Hydrazonato and Azomethine Ligands

AbstractMono‐, di or trinuclear dioxouranium complexes with benzoylhydrazonato or azomethine ligands were prepared by reactions of common dioxouranium precursors such as UO2(NO3)2 · 6 H2O or [NBu4]2[UO2Cl4] with vanillin benzoylhydrazone (H2L4), salicylaldehyde benzoylhydrazone (H2L5), 2‐hydroxyacetylbenzene salicylhydrazone (H3L6) or N‐(2‐ethoxycarbonyl‐3‐oxo‐but‐1‐en(1)yl)‐2‐aminophenol (H2L7).Spectroscopic and X‐ray crystallographic studies on the complexes [NBu4]2[UO2Cl4] · 2 H2L4, [UO2(HL5)(H2L5)2](NO3), [HNEt3]2[{UO2(L6)}2] and [HNEt3]2[{UO2(L7}3O] confirm that the individual donor atom constellation, the size of the potential chelate rings and the acidity of the OH and NH functionalities of the proligands have a strong influence on the structure of the products.

Synthesis and Antimicrobial Activity of the Complexes of 3d-Metals with Substituted Salicylaldehyde Benzoylhydrazones

Synthesis and Antimicrobial Activity of the Complexes of 3d-Metals with Substituted Salicylaldehyde Benzoylhydrazones