2-Hydroxy-3-methoxybenzaldehyde

Synthesis, Characterization, Biomedical Application, Molecular Dynamic Simulation and Molecular Docking of Schiff Base Complex of Cu(II) Supported on Fe3O4/SiO2/APTS.[Pubmed:32368042]

Int J Nanomedicine. 2020 Apr 20;15:2583-2603.

Introduction: Over the past several years, nano-based therapeutics were an effective cancer drug candidate in order to overcome the persistence of deadliest diseases and prevalence of multiple drug resistance (MDR). Methods: The main objective of our program was to design organosilane-modified Fe3O4/SiO2/APTS(~NH2) core magnetic nanocomposites with functionalized copper-Schiff base complex through the use of (3-aminopropyl)triethoxysilane linker as chemotherapeutics to cancer cells. The nanoparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), TEM, and vibrating sample magnetometer (VSM) techniques. All analyses corroborated the successful synthesis of the nanoparticles. In the second step, all compounds of magnetic nanoparticles were validated as antitumor drugs through the conventional MTT assay against K562 (myelogenous leukemia cancer) and apoptosis study by Annexin V/PI and AO/EB. The molecular dynamic simulations of nanoparticles were further carried out; afterwards, the optimization was performed using MM+, semi-empirical (AM1) and Ab Initio (STO-3G), ForciteGemo Opt, Forcite Dynamics, Forcite Energy and CASTEP in Materials studio 2017. Results: The results showed that the anti-cancer activity was barely reduced after modifying the surface of the Fe3O4/SiO2/APTS nanoparticles with 2-Hydroxy-3-methoxybenzaldehyde as Schiff base and then Cu(II) complex. The apoptosis study by Annexin V/PI and AO/EB stained cell nuclei was performed that apoptosis percentage of the nanoparticles increased upon increasing the thickness of Fe3O4 shell on the magnetite core. The docking studies of the synthesized compounds were conducted towards the DNA and Topoisomerase II via AutoDock 1.5.6 (The Scripps Research Institute, La Jolla, CA, USA). Conclusion: Results of biology activities and computational modeling demonstrate that nanoparticles were targeted drug delivery system in cancer treatment.

Trapped Intermediate of a Meerwein-Pondorf-Verley Reduction of Hydroxy Benzaldehyde to a Dialkoxide by Titanium Alkoxides.[Pubmed:31840987]

Inorg Chem. 2020 Jan 6;59(1):880-890.

A series of titanium alkoxides ([Ti(OR)4] (OR = OCH(CH3)2 (OPr(i)), OC(CH3)3 (OBu(t)), and OCH2C(CH3)3 (ONep)) were modified with a set of substituted hydroxyl-benzaldehydes [HO-BzA-Lx: x = 1, 2-hydroxybenzaldehyde (L = H), 2-Hydroxy-3-methoxybenzaldehyde (OMe-3), 5-bromo-2-hydroxybenzaldehyde (Br-5), 2-hydroxy-5-nitrobenzaldehyde (NO2-5); x = 2, 3,5-di-tert-butyl-2-hydroxybenzaldehyde (Bu(t)-3,5), 2-hydroxy-3,5-diiodobenzaldehyde (I-3,5)] in pyridine (py). Instead of the expected simple substitution, each of the HO-BzA-Lx modifiers were reduced to their respective diol [(py)(OR)2Ti(kappa(2)(O,mu-O')(OC6H4-x(CH2O)-2)(L)x] (OR = OPr(i), x = 1, L = H (1a), OMe-3 (2a), Br-5 (3a.py), NO2-5 (4a.4py); x = 2, Bu(t)-3,5 (5a), I-3,5 (6a), ONep; x = 1, L = H (1b), OMe-3 (2b), Br-5 (3b.py), NO2-5 (4b); x = 2, Bu(t)-3,5 (5b), I-3,5 (6b.py)), as identified by single crystal X-ray studies. The (1)H NMR spectral data were complex at room temperature but simplified at high temperatures (70 degrees C). Diffusion ordered spectroscopy (DOSY) NMR experiments indicated that 2a maintained the dinuclear structure in a solution independent of the temperature, whereas 2b appears to be monomeric over the same temperature range. On the basis of additional NMR studies, the mechanism of the reduction of the HO-BzA-Lx to the dioxide ligand was thought to occur by a Meerwein-Pondorf-Verley (MPV) mechanism. The structures of 1a-6b appear to be the intermediate dioxide products of the MPV reduction, which became "trapped" by the Lewis basic solvate.

Vibrational analysis and physical property studies of 6-Methoxy-2-[(E)-phenyliminomethyl]-phenol in the THz, IR and UV-visible spectral regions.[Pubmed:31181507]

Spectrochim Acta A Mol Biomol Spectrosc. 2019 Nov 5;222:117227.

Bulk single crystals of 6-Methoxy-2-[(E)-phenyliminomethyl]phenol were grown after preparing the material by Schiff base condensation of ortho-vanillin alternatively called 2-Hydroxy-3-methoxybenzaldehyde and aniline. The three dimensional molecular and crystal structure of the title compound is confirmed by X-ray diffraction. Molecules crystallized in the orthorhombic crystal system and noncentrosymmetric space group P212121. Geometry optimization, vibrational analysis, Calculation of HOMO-LUMO band gap and molecular hyperpolarizability of the proposed material have been carried out. Terahertz time domain spectroscopic studies have been performed and the refractive index and absorption coefficient of material is calculated in the THz regime. Molecular vibrations responsible for different THz phonon modes are identified with the help of density functional theory based calculations.

o-Vanillin Derived Schiff Bases and Their Organotin(IV) Compounds: Synthesis, Structural Characterisation, In-Silico Studies and Cytotoxicity.[Pubmed:30781445]

Int J Mol Sci. 2019 Feb 15;20(4). pii: ijms20040854.

Six new organotin(IV) compounds of Schiff bases derived from S-R-dithiocarbazate [R = benzyl (B), 2- or 4-methylbenzyl (2M and 4M, respectively)] condensed with 2-Hydroxy-3-methoxybenzaldehyde (oVa) were synthesised and characterised by elemental analysis, various spectroscopic techniques including infrared, UV-vis, multinuclear ((1)H, (13)C, (119)Sn) NMR and mass spectrometry, and single crystal X-ray diffraction. The organotin(IV) compounds were synthesised from the reaction of Ph(2)SnCl(2) or Me(2)SnCl(2) with the Schiff bases (S2MoVaH/S4MoVaH/SBoVaH) to form a total of six new organotin(IV) compounds that had a general formula of [R(2)Sn(L)] (where L = Schiff base; R = Ph or Me). The molecular geometries of Me(2)Sn(S2MoVa), Me(2)Sn(S4MoVa) and Me(2)Sn(SBoVa) were established by X-ray crystallography and verified using density functional theory calculations. Interestingly, each experimental structure contained two independent but chemically similar molecules in the crystallographic asymmetric unit. The coordination geometry for each molecule was defined by thiolate-sulphur, phenoxide-oxygen and imine-nitrogen atoms derived from a dinegative, tridentate dithiocarbazate ligand with the remaining positions occupied by the methyl-carbon atoms of the organo groups. In each case, the resulting five-coordinate C(2)NOS geometry was almost exactly intermediate between ideal trigonal-bipyramidal and square-pyramidal geometries. The cytotoxic activities of the Schiff bases and organotin(IV) compounds were investigated against EJ-28 and RT-112 (bladder), HT29 (colon), U87 and SJ-G2 (glioblastoma), MCF-7 (breast) A2780 (ovarian), H460 (lung), A431 (skin), DU145 (prostate), BE2-C (neuroblastoma) and MIA (pancreatic) cancer cell lines and one normal breast cell line (MCF-10A). Diphenyltin(IV) compounds exhibited greater potency than either the Schiff bases or the respective dimethyltin(IV) compounds. Mechanistic studies on the action of these compounds against bladder cancer cells revealed that they induced the production of reactive oxygen species (ROS). The bladder cancer cells were apoptotic after 24 h post-treatment with the diphenyltin(IV) compounds. The interactions of the organotin(IV) compounds with calf thymus DNA (CT-DNA) were experimentally explored using UV-vis absorption spectroscopy. This study revealed that the organotin(IV) compounds have strong DNA binding affinity, verified via molecular docking simulations, which suggests that these organotin(IV) compounds interact with DNA via groove-binding interactions.

New Coordination Modes for Modified Schiff Base Ti(IV) Complexes and Their Control over Lactone Ring-Opening Polymerization Activity.[Pubmed:30376308]

Inorg Chem. 2018 Nov 19;57(22):14240-14248.

A series of eight new bis(alkoxy)bis(phenoxy-imine)titanium(IV) catalysts, coordinated by Schiff base ligands derived from o-vanillin (2-Hydroxy-3-methoxybenzaldehyde), show good activity and control for the ring-opening polymerization of epsilon-caprolactone and omega-pentadecalactone. The new complexes are easily prepared in two high-yield steps from commercial reagents. The new ligands can all adopt two different coordination modes, depending on the steric bulk on the imine: a six-membered N-O chelate and/or a five-membered O-O chelate. The complexes show three different structures, depending on the ligand coordination mode: type A (N-O:N-O), type B (N-O:O-O), and type C (O-O:O-O). In all cases, the structures were confirmed in solution using variable temperature NMR spectroscopy and in the solid state using X-ray crystallography. The complex structure influences the polymerization rate, with the catalytic activities decreasing in the order: type C > type B > type A for both monomers. Overall, the work demonstrates potential to use these new ligands to access particular coordination modes, which allows enhancement of catalytic activity.

Synthesis, Bacteriostatic and Anticancer Activity of Novel Phenanthridines Structurally Similar to Benzo[c]phenanthridine Alkaloids.[Pubmed:30150591]

Molecules. 2018 Aug 27;23(9). pii: molecules23092155.

In this study, we report the synthesis, antibacterial and anticancer evaluation of 38 novel phenanthridines that were designed as analogs of the benzo[c]phenanthridine alkaloids. The prepared phenanthridines differ from the benzo[c]phenanthridines in the absence of a benzene A-ring. All novel compounds were prepared from 6-bromo-2-Hydroxy-3-methoxybenzaldehyde in several synthetic steps through reduction of Schiff bases and accomplished by radical cyclization. Twelve derivatives showed high antibacterial activity against Bacillussubtilis, Micrococcusluteus and/or Mycobacteriumvaccae at single digit micromolar concentrations. Some compounds also displayed cytotoxicity against the K-562 and MCF-7 cancer cell lines at as low as single digit micromolar concentrations and were more potent than chelerythrine and sanguinarine. The active compounds caused cell-cycle arrest in cancer cells, increased levels of p53 protein and caused apoptosis-specific fragmentation of PARP-1. Biological activity was connected especially with the presence of the N-methyl quaternary nitrogen and 7-benzyloxy substitution (compounds 7i, 7j, 7k, and 7l) of phenanthridine.

Element-Selective Molecular Charge Transport Characteristics of Binuclear Copper(II)-Lanthanide(III) Complexes.[Pubmed:30040402]

Inorg Chem. 2018 Aug 6;57(15):9274-9285.

A series of isostructural dinuclear 3d-4f complexes, isolated as [CuLn(L.SMe)2(OOCMe)2(NO3)]. xMeOH (Ln = Gd 1, Tb 2, Dy 3, and Y 4; x = 0.75-1) and comprising one acetate and two thioether-Schiff base (L.SMe(-)) bridging ligands based on 4-(methylthio)aniline and 2-Hydroxy-3-methoxybenzaldehyde (HL.SMe = C15H15NO2S), was synthesized and fully characterized. The magnetic properties of the charge-neutral {CuLn} complexes are dominated by ferromagnetic Cu(II)-Ln(III) exchange interactions. Large-area electron transport studies reveal that the average conductivity of robust, self-assembled {CuLn} monolayers on a gold substrate is significantly lower than that of common alkanethiolates. Theoretical calculations of transmission spectra of individual complexes 1 and 4 embedded between two metallic electrodes show that the molecular current-voltage ( I- V) characteristics are strongly influenced by electron transport through the Cu centers and thus fully independent of the lanthanide ion, in excellent agreement with the experimental I- V data for 1-4. The beta-polarized transmission indicated by calculations of 1 and 4 points out their potential as spin filters. In addition, the reactivity of the title compound 1 with Cu(II) in a square-pyramidal coordination environment toward methanolate and azide was examined, resulting in the formation of a linear trinuclear complex, [Cu2Na(L.SMe)4]NO3.3MeOH (5), characterized by antiferromagnetic exchange interactions between the two copper ions.

Modulating the Magnetic Interaction in New Triple-Decker Dysprosium(III) Single-Molecule Magnets.[Pubmed:29314838]

Inorg Chem. 2018 Feb 5;57(3):1408-1416.

A new type of dinuclear dysprosium(III) complex based on phthalocyanine and salicylaldehyde derivatives (HL-R), [Dy2(Pc)2(L-R)2(H2O)].2THF (R = OCH3 (1), OC2H5 (2); H2Pc = phthalocyanine; HL-OCH3 = 2-Hydroxy-3-methoxybenzaldehyde; HL-OC2H5 = 3-ethoxy-2-hydroxybenzaldehyde), was successfully synthesized and structurally characterized. Complex 1 features a sandwich-type triple-decker structure, where two coplanar L-OCH3 ligands lie in the middle layer shared by two eight-coordinated Dy(III) ions and two Pc ligands are located in the outer layer. In 2, the introduction of an ethoxy group generates a noncoordination mode for the Oalkoxy atom. Magnetic studies indicate that complex 1 behaves as a zero-field single-molecule magnet with a higher energy barrier, while 2 exhibits a fast tunneling relaxation process. Theoretical calculations revealed that changes in the ligand field environment around Dy(III) ions can significantly affect the arrangement of the main magnetic axes and further result in distinct magnetic interactions as well as different relaxation behaviors.

Anti-proliferative effect of Fe(III) complexed with 1-(2-hydroxy-3-methoxybenzaldehyde)-4-aminosalicylhydrazone in HepG2 cells.[Pubmed:25850340]

Biometals. 2015 Aug;28(4):669-77.

We previously developed a chelating ligand, 1-(2-Hydroxy-3-methoxybenzaldehyde)-4-aminosalicylhydrazone (HMB-ASH), which can chelate Fe(III) to form a complex. The HMB-ASH-Fe(III) complex exhibits a dose-dependent anti-proliferative effect in HepG2 cells, whereas the ligand, HMB-ASH, and Fe(III) alone had no considerable effect. The HMB-ASH-Fe(III) complex was composed of Fe(III):HMB-ASH (1:2), as determined by high-performance liquid chromatography with high-resolution mass spectrometry. The IC50 value was approximately 20 muM, which was comparable to those of the anti-cancer drugs oxaliplatin (OXP) and etoposide (ETP) under the same conditions. Similar to OXP and ETP, HMB-ASH-Fe(III) induced apoptosis in HepG2 cells, as revealed by terminal deoxynucleotidyl transferase fluorescein-12-dUTP nick end labeling assay.